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Supplementary Figure 1. Sabates-Bellver et al.

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Supplementary Figure 1. Unsupervised hierarchical clustering of normal colonic mucosa (32 samples, green branches), colorectal adenomas (32 samples, red branches), and advanced colorectal carcinomas (25 samples, black branches) based on transcriptome analysis with Affymetrix U133 Plus 2.0 arrays. Data were analyzed as described in Methods. The 32,813 probes plotted on the y-axis (i.e., those expressed in at least one of the three tissue groups) are color-coded to indicate their expression levels relative to the median level for the across the entire sample set (blue: lower; red: higher). As expected, the tissue sample collected from patient NM’s polyp (*) clustered with the adenomas. This sample was clearly adenomatous although the polyp itself was classified as a T1 tumor (Table 1). Supplementary Figure 2; Sabates-Bellver et al. A B mitosis humoral defense mechanism

CDC25B CCR2 CDC2 CCL14 CCNF C7 RAN CCL14 CDCA5 TNFRSF17 MAD2L1 CLU MAD2L1 CR2 CCNB1 C1S PRMT5 TNFRSF7 BUB1B SERPING1 PBK CD53 TPX2 KLRK1 BUB1 LY9 CDC2 CSF1R MAD2L2 KLRC4 CDC20 CLEC2B CDC6 C1QC UBE2C C1QA NUSAP1 C1QB AURKA HHEX BUB1 C1S CDC2 KLRC1 CCNA2 KLRD1 HCAP-G ITGB2 PTTG1 SPINK5 SMC2L1 HHEX PLK1 CD163 CCNA2 CCR2 KNTC2 MAG NEK2 CD163 KIF2C C3 BRRN1 XCL1 CCNB2 XCL2 NOLC1 ITGB2 KIF23 KLRB1 HCAP-G SLAMF1 KIF2C KLRD1 RCC1 LY9 AURKA CLEC2D CCNB1 CD1C CDC25C CD53 KIF11 CR1 ASPM CD74 CDC6 IGSF2 NEK2 CLEC2D KIFC1 CLU CDC25C CLU CENPE CCL18 NUSAP1 KLRF1 CDC25A CCL18 CCNF CR1 CDC25A CD40 CDC2 CCR7 adenomas normals CCR6 adenomas normals C D inflammatory response inflammatory response

IL8 CCR2 ALOX5 NR3C1 IL8 NR3C1 MIF NR3C1 CXCL11 CXCL12 CXCL3 NR3C1 RIPK2 NR3C1 TLR4 AOC3 CXCL1 CD14 CXCL11 TLR7 CXCL2 STAB1 PF4 CXCL13 TLR4 CCL23 TLR4 HDAC9 CCL20 CCL21 TLR4 CCL5 CCL24 CCL5 S100A8 LY86 ALOX5 ITGAL S100A9 CCL23 REG3A CCL8 ANXA1 STAB1 SERPINA3 CCL5 IL1B CXCL12 IL1B CCL19 CCL26 BDKRB1 adenomas normals IL1R1 SIGLEC1 ADORA3 CCL2 PREX1 TLR3 Supplementary Figure 2. Tile plots TLR8 showing differential expression in C3AR1 adenomas (vs. normal mucosa) of ITGB2 involved in mitosis, humoral PREX1 defense, or inflammatory response. AIF1 Mitosis (A) was the biological process CCR2 category most significantly over- TLR7 represented among genes that were TLR10 overexpressed in adenomas; humoral CCL13 defense mechanisms (B) predominated C3 among those that were under-expressed ITGB2 in adenomas. The category AIF1 inflammatory response was AIF1 overrepresented in both gene lists KNG1 (over- and under-expressed in LY96 adenomas) (panels C and D). Red tiles: CCL18 high expression; green tiles: low TLR10 expression. For genes listed in gray, CCL18 two or more probes were differentially CD40 CCR7 expressed. adenomas normals Supplementary Figure 3, Sabates-Bellver et al.

A 2.5 y t i

s 2.0 n e t

n 1.5 I

d e

z 1.0 i l a m

r 0.5 o N 0.0 Normal Mucosa Adenomas Samples

B Ct KIAA1199_Co >31 22 >31 KIAA1199 Ad 20 KIAA1199_NM 18 KIAA1199_NM >31 GAPDH NM & Ad 16 25.3

e KIAA1199_Ad c

n 14 KIAA1199_Ad 24.8 e

c 12 s GAPDH_Co >31 e

r 10 o GAPDH_NM 20.5 u

l 8 F

GAPDH_NM 20.9 6

KIAA1199 NM 4 GAPDH_Ad 20.5

2 GAPDH_Ad 19.6 Co 0 -2 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 Cycles of amplification

C KIAA1199 GAPDH

M Co NM Ad NM Ad M Co NM Ad NM Ad

200 bp

Supplementary Figure 3. KIAA1199 messenger RNA expression in colorectal adenomas. (A) KIAA1199 mRNA levels detected in samples of normal colorectal mucosa and adenomas with the Affymetrix U133 Plus 2.0 array based on normalized raw signal values (y-axis). Levels in adenomas were 54.8 times higher than those found in the normal mucosa. This difference was highly significant (p < 0.0001; bars: confidence intervals). (B) Real-time RT-PCR amplification of the coding region of KIAA1199 and the control housekeeping gene GAPDH in two representative adenomas and matched samples of normal mucosa. (A total of 15 tissue pairs were examined in triplicate, including five collected after the present study was completed.) Ct (threshold cycle): number of cycles (x-axis) at the beginning of the log phase of amplification. After 35 cycles of PCR, KIAA1199 was amplified in adenomas but not in the corresponding normal mucosa. At 40 cycles, a PCR product was also detected in many samples of normal mucosa (data not shown). (C) The KIAA1199 amplification products were subjected to agarose-gel electrophoresis to verify the specificity of the amplification. M: 50-bp ladder marker; Co: negative control; NM: normal mucosa; Ad: adenoma.

Sabates-Bellver et al. Supplementary Figure 5

Homsap-KIAA1199-38638698 PVRPKLTVTIDTNVNS---TILNLEDNVQSWKPGDTLVIASTDYSMYQAEEFQ---VLPCRSCAPNQVKVAGKPMYLHIGEEIDG------VDMRAEV Musmus-9930013L23Rik-38638700 PVRPKLTVSIDTNVNS---TILSLVDNVRSWRPGDTLVVASTDYSMYQAEEFR---VLPCKACTSTQVKVAGKPQYLHIGEEIDG------VDMRAEV Bostau-LOC519047-76647117 PVRPKLTVTIDTNVNS---TILHLEDNVQSWKPGDTLVVASTDYSMYQAEEFQ---VLPCRTCAPNQVKVAGKPMYLHIGEEIDG------VDMRAEV Homsap-TMEM2-7019555 IEGVSLSGFRVEVVDG---VKLNLLDDVSSWKPGDQIVVASTDYSMYQAEEFT---LLPCSECSHFQVKVKETPQFLHMGEIIDG------VDMRAEV Musmus-TMEM2-76253926 SQGISLSGFRVDIADG---VKLHLLDDVSTWEAGDRIVVASTDYSMYQAEELT---LLRCPECSRSQVKVKEIPQYLHVGEIIDG------IDMRAEV Bostau-LOC515491-76624402 KEGISFSGFWVEAIDG---VKLHLLDDVSSWEPGDQIVVASTDYSMYQAEEFT---LLPCPECSRFQVKVKETPQFLHMGEIIDG------VDMRAEV Canfam-LOC484171-73946811 IEGVSLSGFRVEVVDG---VKLHLLDDVSSWNPGDQIVVASTDYSMYQAEEFT---LLPCPECNRFQVKVKEAPQFLHMGEIIDG------VDMRAEV Danrer-LOC566851-68360196 SNGYPTTGFQVDAVDK---VVLNLQDDVSSWNPGDRIVVASTDYSMYQAEEFT---LLPCPNCNRKQVQIQGKPQFSHVGEILDG------VDMRAEV Homsap-PKHD1-25777665-N LPEVIVTCLRATAHAL---DTVLALEDAVDWNPGDEVVIISGTGVKGAKPMEE---IVTVETVQDTDLYLKSPLRYSHNFTENWVAG----EHHILKATV Musmus-PKHD1-41350424-N VPEVTVTYLQAAAHAG---DKVLTLGEAVDWKPGDEAVITSGMTVAGAEATEV----VVVETVHNADLHLRNPLRYSYDFRENWVAGE----NPILKPSV Canfam-LOC474934-73973294-N LPEVTFTHLQAAAYAG---DTVLALEDAVDWHPGDEAVIISRIGVGGAKPMEE---IVIVEAVHNTDLYLRSPLRYSHNFTENWVAG----VLHILKVTV Strpur-LOC582056-72006337-N PVPIMWTHLSETIDPE---DTDISLMRPVTWNVGDQIVIATTGGRLDIDQNEVV--TITAVSDDNMTLTVDPPIEYQHISIVQDIAG----VILETRAEV Homsap-PKHD1L1-29150259-N PVPVTWTRLAHTAKAG---ERILILQEAVTWKPGDNIVIASTGHRHSQGENEKM--TIASVSADGINITLSNPLNYTHLGITVTLPDG---TLFEARAEV Musmus-PKHD1L1-29135339-N PIPVVWTRLTHTANAG---EWTLTVQEAVTWKAGDNIVIASTGHRHSQAENEKR--TIASVSADGMHITLTKPLNYTHLGITTTLPDG---TVFEARAEV Canfam-LOC475075-73974520-N PVSVIWTHLAHTAKAG---ERTLILQEAVTWKPGDKIVIASTGHRHSQQENEKR--TIASVSADGTNILLTNPLNYTHLGTTVTLPDG---TLFEARAEV Tetthe-89301608 LRPVTWTELSQTAKIGDTSIQVFIKDPGFDWKIGEEIVIASTDFAHSHAERRVITNVQKSGDGKYVTISFLDPLLSQHISITGESYQG-GRKLVNMRAEV Tetthe-89301609 LRPVTWTELSQTAKIGDTSIQVFIKDPGFDWKTGEEIVIASTDFAHGHAERRVITNVQKSGDGKYVTISFSDPLLVQHVSITGESYQG-GKKLVNMRAEV Tetthe-89289159 PRAVTWTELSQTANIGDNSIQVFLKDSAFDWQVGEEIVIASTDYADGHAERRIITNVVRNKDGTTATISFFNPLLAQHVSVSNEQYAS-GLFSVNMRAEV Tetthe-89289160 PRAVTWTELSQTANIGDNSIQVFLKDSAFDWQIGEEIVIASTDYADGHAERRIITNILIIRMEQLQQ------QVSLIPY-LPNIVNMRAEV Tetthe-89289217 TRAVTWTELSATANVGETSIQVFMNDPAFDWQIGEEIVIASTDYVDGHSERRIITNISKNADGKTVTISFVQPLLVQHVSVTGESYKS-GQFLVNMRAEV Tetthe-89301610 PRPVTWTELSSTAKIGDTSIKVFLKDPGFDWKQGEEIVIAPTDYSAGHAERRVITNVVKNADGLTATISFYEPLLIQHVSVENEQYANG-NFKVNMRAEV Homsap-PKHD1-25777665-C YPKNSWTHLGADIASG---NERIIVEDAVDWRPHDKIVLSSSSYEPHEAEVLT------VKEVKGHHVRIYERLKHRHIGSVHVTEDG---RHIRLAAEV Musmus-PKHD1-41350424-C YPKKSWVHLGADIAPG---NERIIVHNAVDWQPHDTIVLSSSSYEAHEAEVLT------VKEVKGHHIRIYERLKHRHIGSTHIMEDG---QQIHLAAEV Canfam-LOC474934-73973294-C CPKKSWTRLAADIASG---NERIIVEDAVDWRPHDKIVLSSSSYEPHEAEILT------VKEVQAHHVKIYERLKYRHIGSVHVMEDGR---CIRLAAEV Homsap-PKHD1L1-29150259-C PHSIYKTKLSETAFAG---SKVLSLMDAVDWQEGEEIVITTTSYDFHQTETRS----IVKILHDHKILILNDSLSYTHFAEKYHVPGTG--ESYTLAADV Musmus-PKHD1L1-29135339-C PHSVYKTKLLETAEAG---SKILSLVDAVDWQEGEDVVITTTSYDLHQTEIRR----IAKILHGHKILILNDSLSYTHLAERQWISG--TAQSYTLSADV Canfam-LOC475075-73974520-C PRSIYKTKLSETAEAG---SKVLSLVDAVDWQEGEEIVITTTSYDFHQTETRS----IIKILHDQKILILNDTLSYTHLAERYHVPGTG--QSYTLAADV Strpur-LOC582056-72006337-C APEVTWTHLAMTVSPG---DNSISLEKDTNWKVGDEIAVATTDYETWHTETFA-----IQEVTDARTFVLNATFQHLHTAATEHENTQN---QYRIAAEV

Homsap-KIAA1199-38638698 GLLSRNIIVMGEMEDKCYPYRN------HICNFFDFDTFGGHIKFALGF-----KAAHLEGTELKHMGQ-----QLVGQYPIHFHL Musmus-9930013L23Rik-38638700 GLLTRNIVVMGEMEDRCYPYTN------HICDFFDFDTFGGHIKFALGF-----KAAHLEGVELKYMGQ-----QLVGQYPIHFHL Bostau-LOC519047-76647117 GLLSRNIVVMGEMEAECYPYSN------HLCNFFDFDTFGGHIKFALGF-----KAAHLEGVELKHMGQ-----QLIGQYPIHFHL Homsap-TMEM2-7019555 GILTRNIVIQGEVEDSCYAEN------QCQFFDYDTFGGHIMIMKNF-----TSVHLSYVELKHMGQ-----QQMGRYPVHFHL Musmus-TMEM2-76253926 GLLTRNIVIQGEMEDSCYAENH------CQFFDYDTFGGHVMIEKNF-----TSVHLSYVELKHMGQ-----QHMGRYPVHFHL Bostau-LOC515491-76624402 GILTQNIVIRGEMEDSCYAEN------QCQFFDYDTFGGHVMIKKNF-----TSVHLSHVELKHMGQ-----QHLGRYPVHFHL Canfam-LOC484171-73946811 GILTRNILIRGEMEDSCYAGN------QCQFFDYDTFGGHVMIRKNF-----TSVHLSYVELKHMGQ-----QELGRYPVHFHL Danrer-LOC566851-68360196 ALLSRNILIHGEMENSCYGGN------WCQYFSYDTFGGHIKILGNF-----TSVHLSHIELKHMGQ----QREKGRYPLNFHR Homsap-PKHD1-25777665-N ALLSRSITIQGNLTNEREKLLVSCQEAN--APEGNLQHCLYSMSEKMLGSRDMGARVIVQSFPEEP--SQVQLKGVQFQVLGQ------AFHKHL Musmus-PKHD1-41350424-N ALLSRNIIIQGNFTLERVKLLNSCQEANTAKG--NLKHCLYSKSEKMLGARDLGARVIIQSFPEEP--SFVKLKGVQFRDLGQ------AFHKHLSSLAL Canfam-LOC474934-73973294-N VLLSRSITIQGNLTAERMKHLASCQEASD--SEGNLQDCLYSKSEKMLGSRDLGARVIVQSFPEEP--SRVQLRGVQFRDLGQ------AFRKHVSALTL Strpur-LOC582056-72006337-N GLLTHNVVVRGNVNEDWTEEIEACEAPFDTG-MFDTQTCFLGRFGEETASDQFGGHIMIFAREMDANLVHGYLEYVELTHVGQ----AFRLGRYPIHYHM Homsap-PKHD1L1-29150259-N GILTRNILIRGSDNVEWNNKIPACPDGFD-TGEFATQTCLQGKFGEEIGSDQFGGCVMFHAPVPGANMVTGRIEYVEVFHAGQ----AFRLGRYPIHWHL Musmus-PKHD1L1-29135339-N GILTRNILIRGSDNVEWNDKIPSCPDGFD-TGEFATQTCLQGKFGEEMGSDQFGGCIMLHAPLPGADMVTGRIEYVEVFHAGQ----SFRLGRYPIHWHL Canfam-LOC475075-73974520-N GILTRNILIRGSDHVEWSNKIPACPDGFDTG-EFTTQTCFQGKFGEETGSDQFGGCIMFHAPIPSANMVIGRIEYVEIFHAGQ----AFRLGRYPIHWHL Tetthe-89301608 GLLTRNVVYEGDDSSIQT------QYGAHLMLHGSK-----ASARIRHTEFRHTGQ----PAIIGRYPIHFHM Tetthe-89301609 GLLTRNVVYEGDDSSIQT------QYGAHLMLHGSK-----TSARIRYAEFRHTGQ----PAIIGRYPIHFHM Tetthe-89289159 GLLTRNVVFEGDDSSVQT------QYGAHLMLHGSQ-----TSARIRFAEFRRTGQ----PAIIGRYPIHFHM Tetthe-89289160 GLLTRNVVFEGDDSSVQT------QYGAHLMLHGSQ-----TSARIRFAEFRRTGQ----PAIIGRYPIHFHM Tetthe-89289217 GLLTRNVVFEGDQSSIAT------RYGAHLMLHGSQ-----TSARIRYAEFRYTGQ----PAIIGRYPIHFHM Tetthe-89301610 GLLTRNVVFEGDDSSVKT------QYGAHMMLHGSQ-----TSAHIRFAEFRHTGQ----PAIIGRYPIHFHM Homsap-PKHD1-25777665-C GLLTRNIQIQPDVSCRGRLF------VGSFRKSSREEFS------GVLQLLNVEIQNFGS------PLYSSVEFSN Musmus-PKHD1-41350424-C GLLTRNIRIQPDSSCRGRLL------VGSFRKSSGEDFS------GVLQLLNVEIQNMGL------PLYSSIEFTG Canfam-LOC474934-73973294-C GLLTRNIQIQPDISCRARLL------VGSFRNSSSKEFS------GVLQLSNVEIQNFGS------PLYSSIEFTN Homsap-PKHD1L1-29150259-C GILSRNIKIVGEDYPGWSEDSFG------ARVLVGSFTENMMTFK------GNARISNVEFYHSGQEGFRDSTDPRYAVTFLN Musmus-PKHD1L1-29135339-C GILSRNIKIVGDDYSVLSKDSFG------ARILVGSFTGNMMTFK------GNARISNVEFHHSGQEGYRDSTDPRYAVTFLN Canfam-LOC475075-73974520-C GILSRNIKILGEDYPGWFKESFG------ARVLVSSFTQDMMTFK------GNARISNVEFYHSGQEGFRDNTDPRHAVTFLN Strpur-LOC582056-72006337-C GLFTRNIVIEGASYDGIFTELFG------ARVLVGSFYQDQDFFQ----GRAYISNVQFKHTGQEGYVESYDPRFSVAFLD

Homsap-KIAA1199-38638698 AGDVDERGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKMITEDSYPGYIP Musmus-9930013L23Rik-38638700 AGDLDEQGGYDPPTYIRDLSIHHTFSRCVTVHGSNGLLIKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSRMCKVITEDSYPGYIP Bostau-LOC519047-76647117 AGDVDEKGGYDPPTYVKDLSIHHTFSRCVTVHGSNGLLVKDVVGYNSLGHCFFTEDGPEERNTFDHCLGLLVKSGTLLPSDRDSKMCKTITEDSYPGYIP Homsap-TMEM2-7019555 CGDVDYKGGYRHATFVDGLSIHHSFSRCITVHGTNGLLIKDTIGFDTLGHCFFLEDGIEQRNTLFHNLGLLTKPGTLLPTDRNNSMCTTMRDKVFGNYIP Musmus-TMEM2-76253926 CGDVDSKGGYSQPASVDGLSVHHSFSRCITVHGTSGLLIKDTIGFDTLGHCFFLEDGVEQRNILYHNLGLLTKPGTLLPTDRNSSMCTVMRDGVFGNYVP Bostau-LOC515491-76624402 CGDVDYKGGYRHATFVDGLSIHHSFSRCITVHGTNGLLIKDTVGFDTLGHCFFLEDGLLAFGDMFSG------Canfam-LOC484171-73946811 CGDVDYKGGYSPATFVDGLSIHHSFSRCITVHGTNGLLIKDTIGFDTLGHCFFLEDGVEQRNILFHNLGLLTKPGTLLPTDRNNSMCTTMRDKVFGNYVP Danrer-LOC566851-68360196 CGDVDQSGGYSNPAYVDSLSIHHSFSRCVTVHATNGLLVKDTVGYDTLGHCFFLKDGIEQRNIFFHNLGLLTRPGTILPTDRNDSMCTEITDRVYKGYIP Homsap-PKHD1-25777665-N SSLTLVGAMR--ESFIQGCTVRNSFSRGLSMCGTLGLKVDSNVFYNILGHALLVGTCTEMRYISWEAIHGRKDDWSGHGN-----IIRNNVIIQVSGAEG Musmus-PKHD1-41350424-N VGAMRG------SYIQSCSVWNSFSRGLSMHRTWGLKVDSNVFYKIVGHALLLGLPTWTEGLALVRLLLEEKNGWWEQG----STIRNNVIISVSAAEG Canfam-LOC474934-73973294-N VGAMRD------SYVQGCTVWSSFNRGLSMSMTLGLKVDSNIFYNILGHALLVGTDMDIKYISWEAAPEKKPDWSEQGN-----IIRNNVIISISGTEG Strpur-LOC582056-72006337-N NGDVSG------SYVRGCSVHHTFNRAVTIHGVHNLLVEHNVAYNIMGHAYFMEDGIETNNTIQYNLAVFVRSSNSLLN------Homsap-PKHD1L1-29150259-N LGDLQFK------SYVRGCAIHQAYNRAVTIHNTHHLLVERNIIYDIKGGAFFIEDGIEHGNILQYNLAVFVQQSTSLLN------Musmus-PKHD1L1-29135339-N LGDLQFK------SYVKGCAIHQSYNRAITIHNTHHLLVERNIIYDIKGGAFFIEDGIEHGNILQYNLAVFVQQSTSLLN------Canfam-LOC475075-73974520-N LGDLQFK------SYVKGCAIHQTYNRAVTIHNTHHLLVERNIIYDIKGGAFFIEDGIEHGNILQYNLAVFVQQSTSLLN------Tetthe-89301608 VGDVSG------SIVEGNAVHDSFARVLTIHATHYLHVKNNVGYNCAGHNIFLEDGIETNNVIEENLIIGTRQVWS------Tetthe-89301609 VGDVSG------SIVEGNAVHDSFARVLTIHATHYLHVKNNVGYNCAGHNIFLEDGIETNNVIEENLIIGTRQVWS------Tetthe-89289159 VGDVSG------SIVEGNAVHDSFARVLTIHATHYLHVKNNVGFNCAGHNIFLEDGIETNNIIEQNLILGTKQVWS------Tetthe-89289160 VGDVSG------SIVEGNAVHDSFARVLTIHATHYLHVKNNVGFNCAGHNIFLEDGIETNNIIEQNLILGTKQVWS------Tetthe-89289217 VGDVSG------SVVEGNAIHDSFARAVTIHATHYLHVKNNVAFNNAGHNIFLEDGIETNNLIEYNLILGTIQVWS------Tetthe-89301610 VGDVSG------SIVEGNAVHDSFARVLTIHATHYLHVKNNVGFNCAGHNIFLEDGIETNNIIEQNLILGTKQVWS------Homsap-PKHD1-25777665-C VSAG------SWIISSTLHQSCGGGIHAAASHGVLLNDNIVFGTAGHGIDLEG---QAYTVTNNLVVLMTQPAWS------Musmus-PKHD1-41350424-C VSAG------SWVISSTVHQSCSVGIHASSSHGVILTDNVVFGTNGHGIDVEG---QNYSLTNNLVILTMQSANSSP------Canfam-LOC474934-73973294-C ASAG------SWIISSSLHQSCSGGIRAAASHGIILNDNIVFGTVGHGIDLEG---QNFSLSNNLVVLMTQSAWS------Homsap-PKHD1L1-29150259-C LGQIQEHG----SSYIRGCAFHHGFSPAIGVFGTDGLDIDDNIIHFTVGEGIRIWG---NANRVRGNLIALSVWPGTYQNR------K Musmus-PKHD1L1-29135339-C LGQIQDHG----LSYVRGCAFHHVFSPAIGVFGTDGVDIDDNIIYFTVGEGIRIWG---DANRVRGNLVTLSVWPGTYQNR------K Canfam-LOC475075-73974520-C LGQIQERG----SSYIRGCAFHNGFSPAIGVFGTDGLDIDNNIIHFTVGEGIRIWG---DANRVRGNLVVLSVWPGTYQNK------K Strpur-LOC582056-72006337-C LRDPFFNTL---PSSLTGCSFHHGFSTAIGAYSSNKLIIKDNIVHHTIGAGIIIEG--SEDILLEHNLVMLSISKATYQDR------W

Homsap-KIAA1199-38638698 KPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSII- Musmus-9930013L23Rik-38638700 KPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSVGMYSPGYSEHIPLGKFYNNRAHSNYRAGMIIDNGVKTTEASAKDKRPFLSII- Bostau-LOC519047-76647117 KPRQDCNAVSTFWMANPNNNLINCAAAGSEETGFWFIFHHVPTGPSAGMYSPGYSEHIPLGKFLNNRAHSNYRAGMIIDNGVKTTQASAKDKRPFLSII- Homsap-TMEM2-7019555 VPATDCMAVSTFWIAHPNNNLINNAAAGSQDAGIWYLFHKEPTGESSGLQLLAKPELTPLGIFYNNRVHSNFKAGLFIDKGVKTTNSSAADPREYLCLDN Musmus-TMEM2-76253926 VPTTDCMAVSTFWIAHPNNHLINNAAAGSQDAGIWYLFHKEPTGESSGLQLLEKPELTPLGIFYNNRVHSNFKAGLFVDKGVKTTNASASDPREYLCLDN Bostau-LOC515491-76624402 ------RAVSTFWIAHPNNNLINNAAAGSQDAGIWYLFHKEPTGESSGLQLLAKPELTPLGIFYNNRVHSSFKAGLFIDKGVKTTNASAADPREYLCLDN Canfam-LOC484171-73946811 VPATDCMAVSTFWIAHPNNHLISNAAAGSQDAGIWYLFHKEPTGESSGLQLLAKPELTPLGIFYNNRVHSSFKAGLFIDKGVKTTNASAADPREYLCLDN Danrer-LOC566851-68360196 IPANECKAVSSFWIAHPNNHLISNSAAGSQDAGIWYVFHNSSTGDSHGMISETKAELTPLGTFFNNRVHSNFKAGLFIDRKVKSTNATAADPREYLCLDN Homsap-PKHD1-25777665-N LSNPEMLTPSGIYICSPTNVIEGNRVCG---AGYGYFFHLMTNQTS------QAPLLSFTQNIAHSCTRYGLFVY------Musmus-PKHD1-41350424-N LSGSEMLAPAGIYTFSPTNVMEGNRVCA---AGYGYVFHLVTSQT------LQAPLLSFNWNTAHSCTRYGLLVY------Canfam-LOC474934-73973294-N LSSPEMLTPSGIYILNPTNVVEGNRVYV---AGLGYFFHLVTSQTS------QAPLLSFTQNIAHSCTRYGLFIY------Strpur-LOC582056-72006337-N ----VDVTPASFWVTNPDNYVRHNAAAGGSHFGFWYNMPEHPGGPS--FTTEVCPRHVPLGEFNNNTAHSFGWYGLWVFPKYHPKVTG------Homsap-PKHD1L1-29150259-N ----DDVTPAAFWVTNPNNTIRHNAVAGGTHFGFWYRMNNHPDGPSYDR--NICQKRVPLGEFFNNTVHSQGWFGMWIFEEY------Musmus-PKHD1L1-29135339-N ----DDVTPAAFWVTNPNNTIRHNAAAGGTHFGFWYRMNDHPDGPSFDR--NICQKRIPLGEFFNNTVHSQGWFGLWIFEEY------Canfam-LOC475075-73974520-N ----DDVTPAAFWVTNPNNTIRHNAAAGGTHFGFWYRMNNHPDGPSYDRN--ICQKRVPLGEFFNNTVHSQGWFGLWIFEEY------Tetthe-89301608 -MLQSDITAASYWITNPLNTVVNNRAAGGDFYGFWYEIKEHPDGPS--ARNDICPQGMALGKFDGNVAHSYDRFGLRIFVLTNLKNPCSP------Tetthe-89301609 -MLQSDITAASYWITNPLNTVVNNRAAGGDFYGFWYEIKEHPDGPS--ARNDICPQGMALGKFDGNVAHSYDRFGLRIFVLTNLKNPCSP------Tetthe-89289159 -MLQSDITAASYWITNPLNYVFNNRAAGGDFYGFWYEIKEHPDGPS--ARNDICPQGMALGQFTNNIAHSYDRFGLRIFVLTNLQYPCQP------Tetthe-89289160 -MLQSDITAASYWITNPLNYVFNNRAAGGDFYGFWYEIKEHPDGPS--ARNDICPQGMALGQFTNNIAHSYDRFGLRIFVLTNLQYPCQP------Tetthe-89289217 -MLQSDITPGSYWITNPLNYVSNNRAAGGDFYGFWYEIKEHPDGPS--ARNDICPQGMGLGLFTNNVAHSYDRFGLRIFVMTNLQYPCN------Tetthe-89301610 -MLQSDITAASYWITNPLNYVFNNRAGGGDFYGFWYEIKEHPDGPS--ARNDICPQGMALGKFTDNIAHSYDRFGLRIFVMTNLQYPCN------Homsap-PKHD1-25777665-C ----TIWVAGIKVNQVKDINLHGNVVAGSERLGFHIRGHKCSS------CELLWSDNVAHSS-LHGLHLYKESGLDN------Musmus-PKHD1-41350424-C ------WVAGIKVNYAEDIILHGNVVAGSERLGFHVGGHGCSS------EVLWSDNVVHSS-LHGLHLYKKHESNN------Canfam-LOC474934-73973294-C ----TVWVAGIKANQAKDINLYGNVVAGSERIGFHIQGHRCSS------PEARWSDNVAHSS-LHGLHLYKENGLDN------Homsap-PKHD1L1-29150259-C DLSSTLWHAAIEINRGTNTVLQNNVVAGFGRAGYRIDGEPCPGQFN------PVEKWFDNEAHGG-LYGIYMN------Musmus-PKHD1L1-29135339-C DLSSTLWHAAIEINRGTNTVLQNNVVAGFGRVGYRIDGEPCSSQAN------SMENWFNNEAHGG-LYGIYMN------Canfam-LOC475075-73974520-C DLSSTLWHAAIEINRGTNTVLQNNVVAGFGRVGYRIDGEPCSSQSN------PMEKWFDNEAHGG-LYGIYMN------Strpur-LOC582056-72006337-C QVENLNWFGSITFDSADNLVMRDNAVAGSEKAGIMMDGEECGVDSRFSQNVVHSALQINSDLHVTNVTLADNKNAICPMFYSPHALTHKKQDRLFQLTN-

Homsap-KIAA1199-38638698 SARYSPHQDADPLKPREPAIIRHFIAYKNQDHGAWLRGG-DVWLDSCRFADNGIGLTLASGGTFPYDDGSK----QEIKNSLFVGESGNVGTEM------Musmus-9930013L23Rik-38638700 SARYSPHQDADPLKPREPAIIRHFTAYKNQDHGAWLRGG-DVWLDSCRFADNGIGLTLASGGTFPYDDGSK----QEIKNSLFVGESGNVGTEM------Bostau-LOC519047-76647117 SARYSPHQDADPLKPREPAIIKHFTAYKNQDHGAWLRGG-DVWLDSCRFADNGIGLTLASGGTFPYDDGSK----QEIKNSLFVGESGNVGTEM------Homsap-TMEM2-7019555 SARFRPHQDANPEKPRVAALIDRLIAFKNNDNGAWVRGG-DIIVQNSAFADNGIGLTFASDGSFPSDEGSS----QEVSESLFVGESRNYGFQG------Musmus-TMEM2-76253926 SARFRPHQDADPEKPRVAAIIDRLIAFKNNDNGAWVRGG-DIIVQNSAFADNGKGLTFASDGSFPSDEGSS----QEVTESLFVGESRNYGFQG------Bostau-LOC515491-76624402 SARFRPHQDGDPEKPRVAALIDRLIAFKNNDNGAWVRGG-DIVVQNSAFADNGIGLTFASDGSFPSDEGSS----QEVSESLFVGESRNYGFQG------Canfam-LOC484171-73946811 SARFRPHQDADPEKPRVAALIDRLISFKNNDNGAWVRGG-DIVVQNSAFADNGIGLTFASDGSFPSDEGSS----QEVSESLFVGESRNYGFQG------Danrer-LOC566851-68360196 SARFRPHESSDPSRPRVAAIIDTLISFKNNDLGAWIRGG-DIIIRNSGFADNGVGLSFASDGSYPKDEGSS----QEVSQSLFIGESRNRGTNG------Homsap-PKHD1-25777665-N -----PKFQPPWDNVTGTTLFQSFTVWESAGGAQIFRSS-NLRLKNFKVYSCRDFGIDVLESDAN------TSVTDSLLLGHFAHKVS------Musmus-PKHD1-41350424-N -----PKFQPPWNNDTGFTLFQNFMVWGSAGGAQIFRSN-NLHLKNFQVYACRDFGIDILESDEN------TLITDSFLLGHFTHKGS------Canfam-LOC474934-73973294-N -----PQFQPPWDDGRGPTLFQNFTVWGSAGGARISRSS-NLHLKNFQVYSCRDFGIDILESDAN------TSVTDSLLLGHFAHKGS------Strpur-LOC582056-72006337-N ------GCNDFESTPAVFANLTVWNTERGAEVVDCG-AVQLHNFVTSDTEQSGLEYQKVTSIQWLGDDGAEGALIKDSVVIGRSDGISGTG------Homsap-PKHD1L1-29150259-N ---FPMQTGSCTSTVPAPAIFNSLTTWNCQKGAEWVNGG-ALQFHNFVMVNNYEAGIETKRILAPYVGGWGETNGAVIKNAKIVGHLDELGMGS------Musmus-PKHD1L1-29135339-N ---FPMQTGSCTSTVPVPAIFNSLTVWNCQKGAEWVNGG-ALQFHNFVMVNNNEAGIETKRILAPYVGGWGESNGAVIKNAKIVGHLDELG------Canfam-LOC475075-73974520-N ---FPMQTGSCTSTVPVPAIFSSLTTWNCEKGAEWVNGG-ALQFHNFVMVNNFEAGIETKRILAPYVGGWGETNGAVIKNAKIVGHLDELGMGS------Tetthe-89301608 -YRDDSKPNPFVDNPSFTITWKNFVSYRNHEDGVLAEEVGNMIFDNFSLLDN-----KQSGFNVYLTNRTD--EEVILRNSLIVGKSLG------Tetthe-89301609 -YRDDSKPNPFIDNPSFTITWKNFVSYRNHEDGVLAEEVGNMVFDNFWLLDN-----KQSGFNVYLTNRTD--EEVILRNSLIVGKSLG------Tetthe-89289159 -YRDDSQPNPFVNNTSFLTTWSNFVSYRNNEDGVLAENVGNMVFNNFTLVGN-----KQSGFNVYLTNRTD--EYVILQNSLIVGQSTG------Tetthe-89289160 -YRDDSQPNPFVNNTSFLTTWSNFVSYRNNEDGVLAENVGNMVFNNFTLVGN-----KQSGFNVYLTNRTD--EYVILQNSLIVGQSTG------Tetthe-89289217 PYRDDTQPNPFVNNTSFTITWSNFVAYRNNEDGVLAEEVGNMIFNNFTLVGN-----KQSGFNSYLTNRTD--EYVILQNSLIVGQSVG------Tetthe-89301610 PYRDDTQSNPFANNPSFTTTWSNFLSYRNNEDGVLAEEVGNMVFNNFTLVGN-----KQSGFNVYLTNRTD--EYVILQNSLVVGQSSG------Homsap-PKHD1-25777665-C ------CTRISGFLAFKNFDYGAMLHVENSVEIENITLVDNTIG-LLAVVYVFSAPQNSVKKVQIVLRNSVIVATSSSFDCIQDKVKPH Musmus-PKHD1-41350424-C ------CTGVSGFMAFKNFDYGAMVQTENSVDIQNITLVDNTVGLLAITYVSSALLSSVS-TVQITLRNSVIVATSSSFDCIHDRKAPQ Canfam-LOC474934-73973294-C ------CTGISGFLAFKNFDYGAMLHVENSVEIENITLVDNSIGLLATVYVSSVPKSHIEN-VQIVLRNSVIIATSSSFDCIQDRVKPR Homsap-PKHD1L1-29150259-C ------QDGLPGCSLIQGFTIWTCWDYGIYFQTTESVHIYNVTLVDNGMAIFPMIYMPAAISHKIS-SKNVQIKSSLIVGSSPGFNCSDVLTNDD Musmus-PKHD1L1-29135339-C ------QDGLPGCSLIQGFTIWTCWDYGIYFQTTESVHIYNVTLVNNGMSIFSMVYMPPSVSHKIS-SKTVKIKNSLIVGSSPEFNCSDVLTNDS Canfam-LOC475075-73974520-C ------QDGLPGCSLIQGFTIWTCWDYGIYFQTTESVHIYNVTLVDNGMAISSMIYMPAAVSHKIS-SKTVQIKSSLIVGSSPGFNCSDVLTNDD Strpur-LOC582056-72006337-C SVISGHSSSFDCDLDEVAPEVASFESKQRAELTPEEGVAGLVLTTYMSALNGAAFFAFRSIHSYPSIGGNN-----QISDVSFINFDDHCGRQG------

Homsap-KIAA1199-38638698 ------MDNRIWGPGGLDHSGRTLPIGQNFPIRGIQLYDGPINIQNCTFRKFVALEGRHTSA------LAFRLNNAWQSCPHNNVTG Musmus-9930013L23Rik-38638700 ------MDNRIWGPGGLDHSGRTLPIGQNFPIRGIQFYDGPINIQNCTFRKFAALEGRHTSA------LAFRLNNAWQSCPHNNVTN Bostau-LOC519047-76647117 ------MDNRIWGPGGLDHSGRTLPIGQNFPIRGIQFYDGPINIQNCTFRKFAALEGRHTSA------LAFRLNNAWQSCPHNNVTN Homsap-TMEM2-7019555 ------GQNKYVGTGGIDQKPRTLPRNRTFPIRGFQIYDGPIHLTRSTFKKYVPTPDRYSSA------IGFLMKNSWQITPRNNISL Musmus-TMEM2-76253926 ------GQNKYMGTGGIDQKPRTLPRNRTFPIRGFQIYDGPIHLTKSTFKKYVPTPDRYSSA------IGFLMKNSWQTTPRNNVSL Bostau-LOC515491-76624402 ------GQNKYVGTGGIDLKPRTLPRNRTFPIRGFQIYDGPIHLTRCTFQKYVPTLDRYTSA------IGFLMKNSWQITPRNNISF Canfam-LOC484171-73946811 ------GQNKYVGTGGIDQKPRTLPRNRTFPIRGFQIYDGPIHLTRCTFKKYVPTPDRYTSA------IGFLMKNPWQITPRNNISL Danrer-LOC566851-68360196 ------GQNKYWGIGGVDGKMRTLPRNKTFPIRGFQINDGPVRIFDSTFRAFSPTADRFTMA------VGFSLKNIWQLTPRNNLSA Homsap-PKHD1-25777665-N ------LCMSSGIKTPKRWELMVSN------TTFVNFDLINCVAIRT------CSDCSQGQGGFTVKTSQ Musmus-PKHD1-41350424-N ------LCMSAGIKTPQRWELT------ISNTTFVNFDDNCVAIRTCS------GCFQGQGGYTVKTRQ Canfam-LOC474934-73973294-N ------LCMSAGIKTPKRWELIISN------TTFVNFDLTDCVSIR------TCSGCSRGQGGFTVKTNQ Strpur-LOC582056-72006337-N ------ENASCTIGGFVSPQSHFVTLDG------VKFINFDRDTCATLR------ACSKCRFEQGGFTTRFRN Homsap-PKHD1L1-29150259-N ------AFCTAKGLVLPFSEGLTVSS------VHFMNFDRPNCVALGVTSISG------VCNDRCGGWSAKFVD Musmus-PKHD1L1-29135339-N ------MGPTFCTSKGLVLPFSQGLTVSS------VHFMNFDRHACVALGVTSITG------VCNDRCGGWS----AKFVG Canfam-LOC475075-73974520-N ------AFCTRKGLVLPFSEGLTVSS------VHFMNFDRPNCVALGVTSITG------VCNERCGGWSAKFVD Tetthe-89301608 ------NPADDSDLENTRGLITPRTDGFR------VESTHFANFDKKMTVFQSCS------FCWNFKKWVQGGKLTKFID Tetthe-89301609 ------NPADDSDLENTRGLITPRTDGFR------VESTHFANFDKKMTVFKSCS------FCWHFKKWVQGGKLTKFID Tetthe-89289159 ------NPALISDLQNTYGAITPRTDGYR------IQNVHFANFIQNMTVFKSCSG------CSNFMLWVQGGKLTLFKG Tetthe-89289160 ------NPALISDLQNTYGAITPRTDGYK------IQNVHFANFIQNMTVFKSCSG------CSNFMLWVQGGKLTLFKG Tetthe-89289217 ------NPADVSDLQSSYGLITPRTDGFK------VQSVHFANFIQNMKVFKSCS------FCWHFKKWVQGGKLTLFSQ Tetthe-89301610 ------NPADVADLQNTYGIITPRTDGYK------VQNVHFANFIPNTIVFKSCS------FCWHFKKWVQGGKLTLFSG Homsap-PKHD1-25777665-C S-ANLTSTDRAPSNPRGGRIGILWPVFTSEPNQWPQEPWHKVRNDHSISGIMKLQDVTFSSFVKSCYSDDLDVCILPNAENSGIMHPITAERTRMLKIKD Musmus-PKHD1-41350424-C S-ANWTSTDRAPSNPRGGRIGILWPVSASEPNAWPQEPWHKVRSHHSVPGIMKLQDVTFSSFVKSCYSNDLDVCILPNEYSTGVMYPITAERTRMLGIKD Canfam-LOC474934-73973294-C SAN-LTSSDRAPSNPRGGRVGILWPIFTSEPNWWPQEPWHRVRNGHSTSGILKLQDVTFSNFVKSCYSDDLDICILPNVENTGIMHPIMAEGTRMLKIKD Homsap-PKHD1L1-29150259-C PNIELTAAHRSPRSPSGGRSGICWPTFASAHNMAPRKPHAGIMSYNAISGLLDISGSTFVGFKNVCSGETNVIFITN----PLNEDLQHPIHVKNIKLVD Musmus-PKHD1L1-29135339-C PDVELTSAHRSSRPPSGGRSGICWPTFASAHNMAPRKPHAGIMSYNAISGLLHVSDSTFVGFKDVCSGETNVIFITN----PLNEDLQHPIHVKNVQLID Canfam-LOC475075-73974520-C PNIELSAAHRSARPPSGGRSGICWPTFASAHNMAPRKPHAGIMSYNAISGLLEISGSTFVGFKNICAVETNVIFITN----PLNEDLQHPIHVKNIQLVD Strpur-LOC582056-72006337-C ------RVFITNAFS------DDATHPTEVQNINLISTSKESLIFIHRPPLNKVNPSD------CVDMDCDGMKKTLIRDLDGS

Homsap-KIAA1199-38638698 -IAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYP--GSYLTKNDNWLVR------HP Musmus-9930013L23Rik-38638700 -IAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDLDGSVSEYP--GSYLTKDDNWLVR------HP Bostau-LOC519047-76647117 -IAFEDVPITSRVFFGEPGPWFNQLDMDGDKTSVFHDVDGSVSEYP--GSYLTKDDNWLVR------HP Homsap-TMEM2-7019555 -VKFG-PHVSLNVFFGKPGPWFEDCEMDGDKNSIFHDIDGSVTGYK--DAYVGRMDNYLIR------HP Musmus-TMEM2-76253926 -VKFG-PQVSLNVFFGKPGPWFEDCELDGDKNSIFHDIDGSVTGYK--DTYVGRMDNYLIR------HP Bostau-LOC515491-76624402 -VKFG-PHVSLNVFFGKPGPWFEDCELDGDKNSIFHDIDGSVTGYK--DAYVGRMDNYLIR------HP Canfam-LOC484171-73946811 -VKFG-PHVSLNVFFGKPGPWFEDCELDGDKNSIFHDVDGSVTGYK--DAYVGRIDNYLIR------HP Danrer-LOC566851-68360196 -LAF-HPSVTLRAFFGRPGDWFEQNDLDGDKNSIFHDLDGSISGYA--DTYVARADNFLIR------HP Homsap-PKHD1-25777665-N -LKFTNSS------NLVAFPFPHAAILEDLDGSLSGKN--RSHILASMETLSA------Musmus-PKHD1-41350424-N -LKFVNSS------NLVAFPFPHAAVLEDLDGSLSGKN--GSHVLASMETLSD------Canfam-LOC474934-73973294-N -LKFINSP------NLVAFPFPHAAILEDLDGSLSGRN--RSHILASMETLSA------Strpur-LOC582056-72006337-N -MEFANAD------NKVGFQWLYEAVFEDMDGSLSGTDG-ATSITPVNDNLPD------D Homsap-PKHD1L1-29150259-N -VQYSHTP------NKAGFRWEHEMVMIDVDGSLTGHK--GHTVIPHSSLLDP------S Musmus-PKHD1L1-29135339-N -IRYFHAP------NKGGFRWEHEAVLIDVDGSLTGHR--GHTVVPHSS-LLD------PS Canfam-LOC475075-73974520-N -IQYFHTP------NKAGFRWEHEVVLVDVDGSLTGHR--GHTVIPHSSLLDP------S Tetthe-89301608 -ISYANINS------NKIFWENWRREIYQDLDGSLSGRGK-PSWITPSGPHLKS------QI Tetthe-89301609 -ISYANINS------NKIFWENWRREIYQDLDGSLSGRGK-PSWITPSGPHLKS------QT Tetthe-89289159 -ISYENISTS------NFMFWDNWRREIYQDLDGTLTGRGS-QVWVTPAGPHLVN------QT Tetthe-89289160 -ISYENISTS------NFMFWENWRREIYQDLDGTLTGRGS-QVWVTPAGPHLVN------QT Tetthe-89289217 -ITYESISTN------NYMYWDNWRREIYQDLDGSLSGKGS-QQWITPAGPHLVNQKS------CQT Tetthe-89301610 -ISYENIQTT------QYMFWENWRREIYQDLDGSLTGRNS-QVWLTPAGLHLIN------QP Homsap-PKHD1-25777665-C KNKFYFPSLQPRKDLGK--VVCPELDCASPRKYLFKDLDGRALGLPPPVSVFPKTEAEWTASFFNAG------TFREEQ Musmus-PKHD1-41350424-C KNKFYFPVLQSSKDLVG--TICPTLVCEYPRKYLFTDLDGRTLGLPPPVSVFPRTEEEWTGSFLNTG------IFREEQ Canfam-LOC474934-73973294-C KNKFYFPPLQARKGLG--ILVCPESDCENPRKYLFKDLDGRALGLPPPVSVFPKTEAEWTGSFFNTG------TFREEQ Homsap-PKHD1L1-29150259-C TTEQSKIFIHRPDISKVNPSDCVDMVCDAKRKSFLRDIDGSFLGNAG--SVIPQAEYEWDGNSQVGIGDYRIPKAMLTFLNGSRIPVTEKAPHKGIIRDS Musmus-PKHD1L1-29135339-C TIEQSKVFIHRPDISKVNPSDCVDMVCDAKRKSFLRDLDGSFLGNS--GSVIPQAEYEWDGNSQLGIGDYRIPKAMLTYLNGSRIPVTEKAPHKGIIRDA Canfam-LOC475075-73974520-C TTEQSKIFIHRPDVSKVNPSDCVDMVCDAKRKSFLRDMDGSFLGDS--GSVIPQAEYEWNGNSQFGIGDYRIPKVMLTFPNGSRIPITEKAPYKGIIRDS Strpur-LOC582056-72006337-C MLGSVGTVVPDSAFEWDGDQRRGLGDYRIPRMALTDHITGDQIDIADKAPNKGIVGTSSSD------

Homsap-KIAA1199-38638698 DCINVPDWRG------AICSGCYAQMYIQAY---KTSNLRMKIIKNDFPSH------PLYLEGALTRSTHYQQYQPVVTLQKGYTIHWD------Musmus-9930013L23Rik-38638700 DCINVPDWRG------AICSGRYAQMYIQAY---KSSNLRMKIIKNDFPSH------PLYLEGALTRSTHYQQYQPVITLQKGYTIHWD------Bostau-LOC519047-76647117 DCINVPDWRG------AICSGRYAQMYIQAY---KTNNLRMKIIKNDFPNH------PLYLEGALTRSTHYQQYQPVITLQKGYTIHWD------Homsap-TMEM2-7019555 SCVNVSKWNA------VICSGTYAQVYVQTW---STQNLSMTITRDEYPSN------PMVLRGIN-QKAAFPQYQPVVMLEKGYTIHWN------Musmus-TMEM2-76253926 NCVNVTKWNA------VICSGTYAQVYVQTW---NTPNLSMIITRDEYPSH------PMVLRGINQRAIS-PQYQPVVMLEKGYTIHWN------Bostau-LOC515491-76624402 SCINVTKWNA------VVCSGSYAQVYVQTW---STPNLTMTITRDEYPDY------PMVLRGIN-QKAAFSQYQPVIMLEKGYTIHWN------Canfam-LOC484171-73946811 SCVNITKWNA------VVCSGSYAQVYVQTW---STQNLTMTITRDEYPSY------PMVLRGINQKAT-FPQYQPVIMLEKGYTIHWN------Danrer-LOC566851-68360196 QCVDMPQWNG------VVCSGKYSQVYIQTQ---AASNLSLSISRDEYPDK------PMVLRGIRTKTSPSQQYQPVLMMGKSYTMHWN------Homsap-PKHD1-25777665-N SCLVNSSFGRVV--HGSACGGGVLFHRMSIGLA-NTPEVSYDLTMTDSRNK------TTTVNYVRDTLSNPRGWMALLLDQETYSLQSEN------Musmus-PKHD1-41350424-N TCLTNASFSQIVP--GSVCGEAVLFHRMSIALA-NSLDVPKNLTITDIGNK------TITVNYVEDTLSNYYGWMALLLDQETYSLQFESP----- Canfam-LOC474934-73973294-N SCLVNLSFSQIVP--GSVCGEDVIFHHMSIGLA-NAPNVSYDLTITDSRNK------TTTVNYVRDTLSNLYGWMALLLDQETYSLQFETP----- Strpur-LOC582056-72006337-N HCTKDDSAYNFGSVPGAVCDSSIALHRFSFN--HAVPESLLYEDAIFTNAHG------ATPVNYHKKRITHPKGWMVTLIDGETYIMSFLT------Homsap-PKHD1L1-29150259-N HCTQEAEWSIGF--PGSVCDASVSFHRLAFNQPSPVSLLEKDVVLSDSFGT------SIIPFQKKRLTHMSGWMALIPNANHINWYFKG------Musmus-PKHD1L1-29135339-N HCTQEPAWSIG--FPGSICDASVSFHRLAFNKP-SPVSLLEKDVVLSDSFG------TSIVPFQKKRLTHMSGWMALIPNANHINWYFKG------Canfam-LOC475075-73974520-N HCSQEAEWSIGFP--GAVCDTTVSFHRLAFNKPSPVTLLEKDVVLSDSFGT------SIVPFQKKRLTHMSGWMALIPNAKHINWYFKD------Tetthe-89301608 ACATTSDENNQWDDG-VICTQQVVRIEFSNP--EKLDDLLTKSLYVKPCDS------NGNPLGGNTDADYYISKTVNIKNHANDLSHGFVGTFLTG Tetthe-89301609 SCATTSDENNQWDDG-VICTQQVVRIEFSNP--EKFDELYTKALYVKPCDS------NGNPLGGNTDTDYYVSKTVKIKNHAHDLQFGFVGTFLTG Tetthe-89289159 ACSTSQDEQTKWNN-AVICSSQIVRIEFSNP--TDPNDFLAKSLFVLPCDN------TGKAIGGAQISDYYVSQTQRILNPAGDLTGGFVGTFLAG Tetthe-89289160 DCSTSQDEKTKWNN-AVICSSQIVRIEFSNP--VDPYEFQTKSLFVLPCDN------TGKAIGGDQISDYYISQTQRILNPAGDLTGGFVGTFLAG Tetthe-89289217 SSQDMIKWNN-----AVICSQQVVRIEFSNP--VDSNNFRSKALYVLPCDS------TGKGYGGTSNTDYYISKSVKIENAAGDLTLGFVGTFLTG Tetthe-89301610 ACTTSQADQTKWNN-AVICTVQVVRVEFSNP--VDSNDFRSKALYVLPCDN------TGKAVGGTKDSDFYISKSVKIENKADDLTLGFVGTFLAG Homsap-PKHD1-25777665-C KCTYQFLMQG------FICKQTDQVVLILDS--ADAIWAIQKLYPVVSVTSGFVDVFS---SVNANIPCSTSGSVSTFYSILPIRQITKVCFM------Musmus-PKHD1-41350424-C KCTFRAMNQG------FFCKQTEHAVLILDN--VDATWTIPKSHPLVSVTNGFVDTFS---IVKDSDLCPPTSSLSTFYSILPTRQMTKVCFP------Canfam-LOC474934-73973294-C KCTYRALIQG------YICKQSDQAILILDN--ADATWAMQKLYPVVSVTRG---FVDTFSSVNADAPCSTSGSASTFYSILPTREITKICFV------Homsap-PKHD1L1-29150259-C TCKYLPEWQS------YQCFGMEYAMMVIES--LDPDTETRRLSPVAIMGNGYVDLINGPQDHGWCAGYTCQRRLSLFHSIVALNKSYEVYFT------Musmus-PKHD1L1-29135339-C TCKYIPEWQS------YQCSGMEYAMMVLES--LDSDTETRRLSPVAIMSNGYVDLINGPQDHGWCAGYTCQRRLSLFHGIVALNKKYEVYFT------Canfam-LOC475075-73974520-C TCKYIPQWQS------YQCFGMEYAMMVIES--LDSDTETRRLSPVAIVSNGYVDLINGPQDHGWCAGYTCQRRLSLFHSIVALNKSYEVYFT------Strpur-LOC582056-72006337-C -CTWTESWQA------FECHNLDHMMFMVES--MDADTETRRISPVALLADGYVDLINGPQDHGWCLGYTCQERISTFNTLVATGLEYELYFT------

Homsap-KIAA1199-38638698 ------QTAPAELAIWLINFNKGDWIRVGLCYPRG Musmus-9930013L23Rik-38638700 ------QTAPAELAIWLINFNKGDWIRVGLCYPRG Bostau-LOC519047-76647117 ------QTAPSELTIWLINFNKGDWIRVGLCYPRG Homsap-TMEM2-7019555 ------GPAPRTTFLYLVNFNKNDWIRVGLCYPSN Musmus-TMEM2-76253926 ------GPAPRTTFLYLVNFNKDDWIRVGLCYPAN Bostau-LOC515491-76624402 ------GPAPKIAFLYLINFNKNDWIRVGLCYPSN Canfam-LOC484171-73946811 ------GPAPRTAFLYLINFNKNDWIRVGLCYPSN Danrer-LOC566851-68360196 ------GPAPRETVLSLINFDQDDWALLGLCYPNE Homsap-PKHD1-25777665-N ------LWINRSLQYSATFDNFAPGNYLLLVHTDLPP Musmus-PKHD1-41350424-N ------WMNRSLQYSATFDSFAPGNYLLIMHRDLPP Canfam-LOC474934-73973294-N ------WISRSLQYSATFGSFAPGNYLLLVHTVLWP Strpur-LOC582056-72006337-N ------NEQLTNISYTGRFDDFEDGDYVLISHNLTQK Homsap-PKHD1L1-29150259-N ------VDHITNISYTSTFYGFKEEDYVIISHNFTQN Musmus-PKHD1L1-29135339-N ------VEHLTNISYTSTFYGFKEEDYVIISHNFTQN Canfam-LOC475075-73974520-N ------VDHITNISYTSTFYGFKEEDYVIISHNFTQN Tetthe-89301608 QIFSVQWELSQIDFTHFSVQLSPYHTGTGASDTVLLRFPYSDF Tetthe-89301609 QIFSVQWELSQIDFTHFSVQLSPYHTGTGASDTVLLRFPYSDF Tetthe-89289159 QIFQVQWELSQIDFTHFSVGLSPYHSGSTAADTILIKFPIKDY Tetthe-89289160 QIFQVQWELSQIDFTHFSVGLSPYHSGSTAADTILIKFPIKDY Tetthe-89289217 QIFQVQWEMSQIDFTHFSIGLSPYHTGTSASDTILIKFPINDF Tetthe-89301610 QIFQVQWELSQIDFTHFSVGLSPYHSGETAADTILLKFPVMDY Homsap-PKHD1-25777665-C ------DQTPQVLRFFLLGNKSTSKLLLAVFYHEL Musmus-PKHD1-41350424-C ------EQTPPFLRFLLLGNQRASKLILAVFYNEI Canfam-LOC474934-73973294-C ------DQTPQVLRFFLLGNRSTSKLLLAVFYHEL Homsap-PKHD1L1-29150259-C ------GTSPQNLRLMLLNVDHNKAVLVGIFFSTL Musmus-PKHD1L1-29135339-C ------GTSPQNLRLMLLNVEHNKAVLVGIFFSTL Canfam-LOC475075-73974520-C ------GTTPQNLRLMLLNVDHKKAVVVGIFFPTL Strpur-LOC582056-72006337-C ------GTNPQGLRLYFLNADDTQTIVVGIWYANP

Supplementary Figure 5. Multiple sequence alignment of the TH domain generated by

PSI-BLAST for the region 406—1087 of the KIAA1199 (flanking sequences were too diverged to be aligned reliably and have been omitted). Sequence names include the abbreviated genus and species names (3 letters each, e.g. Homsap for Homo sapiens), protein name (PKHD1 for polyductin, PKHD1L1 for fibrocystin L ), and the corresponding NCBI Gene Identification (GI) numbers.

N- and C-terminal repeats of the tandem TH domains in PKHD1 and PKHD1L1 are indicated by postfixes

“-N” and “-C” in the sequence names. residues are colored according to similarities of their physico-chemical features. Residues conserved in >50% sequences are highlighted. Supplementary Data

Transcriptome profile of human colorectal adenomas

Sabates-Bellver et al.

In silico analysis of the KIAA1199 protein.

KIAA1199 was first characterized during a microarray screening for genes specifically expressed in the human ear (Abe S. et al. Am J Hum Genetics 2003;

72:73-82), and it is indeed mutated in some subjects with nonsyndromic

(Abe S. et al., J Hum Genet 2003; 48:564-570). KIAA1199 contains 29 and has a total span of approximately 170 kb. The deduced protein encoded by its full- length cDNA sequence contains 1,361 amino acids. The mature 1,331-amino-acid protein has a calculated molecular mass of 150 kD.

According to our sequence analyses and structure predictions, KIAA1199 can be divided into several regions. The first is a stretch of hydrophobic residues located in the N-terminus (around amino acids 8-30), which appeared to be a signal sequence based on one analysis and a transmembrane helix in another (data not shown). The difficulties involved in differentiating between these two hydrophobic structures, which are very similar, are well known. The PHOBIUS method, which was developed specifically for this purpose (Kall L. et al.. J Mol Biol 2004;338:1027-

1036), indicates that residues 1-34 almost certainly constitute a signal

(probability >99.5%), whereas the presence of a regular transmembrane domain is very unlikely. This conclusion is consistent with our immunohistochemical data,

1 which show that KIAA1199 expression is predominantly cytoplasmic. Its presence in the vacuoles of goblet cells in glands with low-degree dysplasia may be the work of the signal peptide. Even after goblet-cell differentiation has been lost (i.e., in high-degree dysplasia), KIAA1199 expression remains higher in the luminal part of the dysplastic cell layers.

Region 50-170 is predicted to form nine β-strands followed by an α-helix, and it is believed to form an independent G8 domain (He Q. et al., Bioinformatics 2006;

Epub ahead of print, Apr 21). The region around amino acids 180-330 appears to be remotely related to region 1200-1361 (i.e., the C-terminus itself). Guo et al. (FEBS

Letters 2006; 580:581-584) have suggested that these two regions form a novel domain, which they call GG. The GG domain is characterized by the presence of two

α-helices, each surrounded by a number of β-strands. Unfortunately, based on our protein fold-recognition analyses, we were unable to assign either the G8 or the GG domain to any of the known three-dimensional fold categories, and their structures thus remain unknown.

The central region of KIAA1199 (amino acids 340-1170) has been labeled the

“TMEM2 Homolog Domain” (Hogan MC. et al., Hum Mol Genet 2003; 12:685-698; hereafter referred to as the TH domain or THD). Using PSI-BLAST (Altschul et al.,

Nucleic Acids Res 1997; 25:3389-3402), we have found THDs in a number of eukaryotic , including TMEM2, polyductin (PKHD1), and fibrocystin L

(PKHD1L1). Interestingly, the latter two proteins both contained duplicate THDs

(Hogan MC. et al., Hum Mol Genet 2003; 12:685-698). We used the conserved

2 section of multiple sequence alignment (Supplementary Figure 5) to compute a phylogenetic tree of the THD family, which is shown in Figure 5.

We also attempted to predict the structure of the THD. Based on secondary structure, it seems to contain mainly β-strands, but it exhibited no significant similarity to domains with known functions. Interestingly, in protein fold-recognition analysis (Kurowski MA & Bujnicki JM. Nucleic Acids Res 2003, 31:3305-3307), the only known three-dimensional structure displaying a good fit with the THD sequence is a single-stranded, right-handed β-helix fold, like that of the crystal structure of pectate (1ru4 in the ). This latter protein, however, contains only 400 amino acids. Fold-recognition analyses of other fragments of the KIAA1199

THD domain that could theoretically form independent domains (i.e., those with up to

500 residues, such as 340-839 or 671-1170) revealed that the THD comprises several

β-helices (like the one in the pectate lyase) or a single long β-helix with a few insertions. Unfortunately, this prediction is not sufficient to provide concrete clues to the function of the THD.

3 Supplementary Table 1: Biological-process categories most significantly over-represented in the set of genes differentially expressed in adenomas (vs. normal mucosa) with fold differences of 2.0 or more (ErmineJ’s overrepresentation analysis) Genes overexpressed in adenomas category Category genes * Altered category genes ^ p-value # Mitosis 137 37 2.51E-20 Cell Division 168 38 2.54E-17 DNA Replication 130 28 3.16E-12 Spindle Organization and Biogenesis 17 11 1.07E-11

Phosphoinisitide-mediated signaling 29 11 4.18E-08 Nucleotide Biosynthesis 50 13 3.49E-07 Family Amino Acid 14 7 7.97E-07 Metabolism DNA Integrity Checkpoint 11 6 2.31E-06 29 9 4.30E-06 Organization and Biogenesis Purine Nucleotide Metabolism 13 6 8.54E-06 One-carbon compound metabolism 27 8 1.87E-05 Cytoplasm Organization and 10 5 2.20E-05 Biogenesis Inflammatory Response 151 20 4.72E-05 Regulation of 114 16 5.15E-05 Genes underexpressed in adenomas Gene Ontology category Category genes * Altered category genes ^ p-value # Humoral Defense Mechanism 94 40 8.49E-19 Antimicrobial Humoral Response 72 31 1.47E-14 Inorganic Anion Transport 96 33 3.72E-12 Organ Development 190 45 6.94E-10 Inflammatory Response 151 35 3.35E-08 Circulation 77 24 3.70E-08 Elevation of Cytosolic Ion 29 14 4.46E-08 Concentration Linked Protein 81 24 9.05E-08 Signaling Pathway Muscle Contraction 81 24 9.46E-08 Taxis 89 25 1.48E-07 Cell Motility 132 31 3.65E-07 Transmembrane Receptor Protein 109 26 2.67E-06 Tyrosine Kinase Signaling Pathway Cell- 186 36 5.54E-06 Cell-cell Adhesion 115 25 2.18E-05 * Number of genes listed in the corresponding Gene Ontology category. Only categories containing 5- 200 genes were considered. ^ Number of category genes that were significantly up- or down-regulated in adenomas # p-value corrected for multiple testing as reported in: Lee HK et al. "ErmineJ: Tool for functional analysis of data sets" BMC Bioinformatics 2005; 6:269 Supplementary Table 2. Expression of Wnt signaling genes# in normal colorectal mucosa and colorectal adenomas.

Gene Gene Name Fold Symbol § Differences Up* Down* Not expressed in normal mucosa and significantly changed in adenomas CST1 cystatin SN 6.9 ETV4 ets variant gene 4 (E1A enhancer binding protein, E1AF) 5.4 FGF18 Fibroblast 18 1.7 FOSL1 FOS-like antigen 1 2.6 IRX3 iroquois protein 3 8.4 LOC283859 hypothetical protein LOC283859 10.5 MMP3 matrix metallopeptidase 3 (stromelysin 1, progelatinase) 33.9 MMP7 matrix metallopeptidase 7 (matrilysin, uterine) 56.9 MSX1 msh homeobox homolog 1 (Drosophila) 8.5 MSX2 msh homeobox homolog 2 (Drosophila) 22.2 SMAD9 SMAD, mothers against DPP homolog 9 (Drosophila) 2.7 SP5 Sp5 factor 5.2 TNFSF9 () superfamily, member 9 2.4 WNT2 wingless-type MMTV integration site family member 2 1.6

Expressed in normal mucosa and changed in adenomas APCDD1 adenomatosis polyposis coli down-regulated 1 7.2 ASCL2 achaete-scute complex-like 2 (Drosophila) 17.3 AXIN2 axin 2 (conductin, axil) 7.3 BIRC5 baculoviral IAP repeat-containing 5 (survivin) 3.2 BMP4 bone morphogenetic protein 4 2.0 CCND1 cyclin D1 2.0 CCND2 cyclin D2 2.6 CD44 CD44 molecule 4.4 CLDN1 claudin 1 9.0 CSNK1E Casein kinase 1, epsilon 2.4 CSNK2A2 casein kinase 2, alpha prime polypeptide 1.5 CSNK2B casein kinase 2, beta polypeptide 1.2 CXXC4 CXXC finger 4 1.7 EDAR receptor 1.7 EPHA1 EPH receptor A1 1.9 EPHA2 EPH receptor A2 1.5 EPHB2 EPH receptor B2 3.1 EPHB3 EPH receptor B3 3.3 EPHB4 EPH receptor B4 2.2 FLJ43934 hypothetical protein LOC644544 1.4 FUSIP1 FUS interacting protein (serine/-rich) 1 1.4 FZD3 homolog 3 (Drosophila) 2.8 FZD6 frizzled homolog 6 (Drosophila) 1.8 FZD7 frizzled homolog 7 (Drosophila) 1.6 GSK3B kinase 3 beta 1.4 HDGF hepatoma-derived growth factor (high-mobility group protein 1-like) 1.6 Supplementary Table 2 (page 2) HIG2 hypoxia-inducible protein 2 2.3 HMGN3 high mobility group nucleosomal binding domain 3 1.3 IGFBP2 -like growth factor binding protein 2, 36kDa 4.8 IL8 8 14.7 LAMC2 , gamma 2 2.0 LEF1 lymphoid enhancer-binding factor 1 1.5 LGR5 -rich repeat-containing G protein-coupled receptor 5 5.8 LOC646927 Hypothetical protein LOC646927 1.5 MET met proto-oncogene ( ) 3.4 MSLN mesothelin 4.7 v-myc myelocytomatosis viral oncogene homolog (avian) 3.2 NKD2 naked cuticle homolog 2 (Drosophila) 1.7 ODC1 ornithine decarboxylase 1 2.3 PITX2 paired-like homeodomain 2 1.5 POP1 processing of precursor 1, ribonuclease P/MRP subunit 1.4 PTTG1 pituitary tumor-transforming 1 2.3 PTTG3 pituitary tumor-transforming 3 1.6 RARG , gamma 1.8 SMAD6 SMAD, mothers against DPP homolog 6 (Drosophila) 1.7 SOX4 SRY (sex determining region Y)-box 4 2.8 SOX9 SRY (sex determining region Y)-box 9 2.7 TCF3 transcription factor 3 (E2A immunoglob. enhancer bind. fact. E12/E47) 2.3 TCF7 transcription factor 7 (T-cell specific, HMG-box) 2.0 TLE1 transducin-like enhancer of split 1 (E(sp1) homolog, Drosophila) 1.6 WNT5A wingless-type MMTV integration site family, member 5A 1.8 ABCB1 ATP-binding cassette, sub-family B (MDR/TAP), member 1 2.6 APC Adenomatosis polyposis coli 2.2 APC2 Adenomatosis polyposis coli 2 1.3 C2orf31 2 open reading frame 31 1.5 CCND3 cyclin D3 1.2 CDX1 caudal type homeobox transcription factor 1 1.2 CSPG2 chondroitin sulfate 2 () 2.1 DAAM1 associated activator of 1 1.9 DAAM2 dishevelled associated activator of morphogenesis 2 2.9 DHRS9 dehydrogenase/reductase (SDR family) member 9 3.2 DKK3 dickkopf homolog 3 ( laevis) 1.5 DRCTNNB1A down-regulated by Ctnnb1, a 2.5 EDA ectodysplasin A 1.8 EDN3 3 11.1 EDNRB type B 1.8 EFNA1 -A1 2.3 EFNA5 ephrin-A5 1.7 EGFR receptor (v-erb-b oncogene homolog, avian) 2.0 EMP1 epithelial 1 2.3 ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin) 2.0 EPHA10 EPH receptor A10 1.5 EPHA3 EPH receptor A3 9.5 EPHA7 EPH receptor A7 5.0 Supplementary Table 2 (page 3) EPHA8 EPH receptor A8 1.3 EPHB6 EPH receptor B6 1.4 FGF9 9 (glia-activating factor) 3.8 FN1 1 4.1 FOSL2 FOS-like antigen 2 1.5 FRZB frizzled-related protein (SFRP3) 2.6 FZD1 frizzled homolog 1 (Drosophila) 2.0 FZD4 frizzled homolog 4 (Drosophila) 1.5 FZD5 frizzled homolog 5 (Drosophila) 2.5 FZD8 frizzled homolog 8 (Drosophila) 2.4 GCG 68.5 HDGFRP3 Hepatoma-derived growth factor, related protein 3 1.7 HHEX homeobox, hematopoietically expressed 2.2 IGF1 insulin-like growth factor 1 ( C) 4.0 ISLR immunoglobulin superfamily containing leucine-rich repeat 2.4 KLF5 Kruppel-like factor 5 (intestinal) 1.5 L1CAM 4.2 LRRFIP2 Leucine rich repeat (in FLII) interacting protein 2 2.6 MAPK10 -activated protein kinase 10 1.9 MGC39518 hypothetical protein MGC39518 1.9 MITF microphthalmia-associated transcription factor 2.2 NIN ninein (GSK3B interacting protein) 1.5 NLK Nemo-like kinase 1.6 POSTN periostin, specific factor 3.8 PPARD peroxisome proliferative activated receptor, delta 1.8 PPP2CB protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform 1.3 PRKCB1 Protein kinase C, beta 1 4.1 PRKCD protein kinase C, delta 1.8 PRKCE Protein kinase C, epsilon 1.5 PRKCH Protein kinase C, eta 1.7 PRKCZ protein kinase C, zeta 1.2 PTTG1IP pituitary tumor-transforming 1 interacting protein 1.6 RET ret proto-oncogene 1.6 RHOU ras homolog gene family, member U 2.2 SFRP1 secreted frizzled-related protein 1 7.6 SFRP2 secreted frizzled-related protein 2 3.9 SLC9A3R1 solute carrier family 9, member 3 regulator 1 2.7 SMAD1 SMAD, mothers against DPP homolog 1 (Drosophila) 1.7 SMAD3 SMAD, mothers against DPP homolog 3 (Drosophila) 1.5 SMAD4 SMAD, mothers against DPP homolog 4 (Drosophila) 1.5 SNAI2 snail homolog 2 (Drosophila) 3.8 SNF1LK2 SNF1-like kinase 2 1.6 SOSTDC1 sclerostin domain containing 1 2.9 TCF2 transcription factor 2, hepatic; LF-B3; variant hepatic nuclear factor 2.1 TCF4 transcription factor 4 2.5 TCF7L1 transcription factor 7-like 1 (T-cell specific, HMG-box) 1.8 TCF7L2 Transcription factor 7-like 2 (T-cell specific, HMG-box) 1.7 TIAM1 T-cell lymphoma invasion and metastasis 1 2.4 Supplementary Table 2 (page 4) TLE3 transducin-like enhancer of split 3 (E(sp1) homolog, Drosophila) 1.6 TLE4 transducin-like enhancer of split 4 (E(sp1) homolog, Drosophila) 1.6 VEGFC vascular endothelial growth factor C 1.5 WNT2B wingless-type MMTV integration site family, member 2B 2.6 WNT5B wingless-type MMTV integration site family, member 5B 1.9 WNT9A Wingless-type MMTV integration site family, member 9A 1.6 ZNF467 protein 467 1.7 ZNF521 zinc finger protein 521 1.7

Expressed in normal mucosa and unchanged in adenomas AES amino-terminal enhancer of split ATOH1 atonal homolog 1 (Drosophila) AXIN1 axin 1 AXUD1 AXIN1 up-regulated 1 BCL9 B-cell CLL/lymphoma 9 BGLAP bone gamma-carboxyglutamate (gla) protein () BTRC beta-transducin repeat containing C9orf126 Chromosome 9 open reading frame 126 CD24 CD24 molecule CDH1 cadherin 1, type 1, E-cadherin (epithelial) CSNK1A1 Casein kinase 1, alpha 1 CSNK1D casein kinase 1, delta CSNK1G1 casein kinase 1, gamma 1 CSNK1G2 casein kinase 1, gamma 2 CSNK1G3 casein kinase 1, gamma 3 CSNK2A1 casein kinase 2, alpha 1 polypeptide CTBP1 C-terminal binding protein 1 CTBP2 C-terminal binding protein 2 CTGF connective tissue growth factor CTNNB1 (cadherin-associated protein), beta 1, 88kDa CTNNBIP1 catenin, beta interacting protein 1 CYR61 -rich, angiogenic inducer, 61 DIXDC1 DIX domain containing 1 DLL1 delta-like 1 (Drosophila) DLL4 delta-like 4 (Drosophila) DVL1 dishevelled, dsh homolog 1 (Drosophila) DVL2 dishevelled, dsh homolog 2 (Drosophila) DVL3 dishevelled, dsh homolog 3 (Drosophila) EDN1 EDNRA endothelin receptor type A EFNA3 ephrin-A3 EFNA4 ephrin-A4 EFNB1 ephrin-B1 EFNB2 ephrin-B2 EP300 E1A binding protein p300 EPHA4 EPH receptor A4 EPHA5 EPH receptor A5 EPHB1 EPH receptor B1 FBXW11 F-box and WD-40 domain protein 11 Supplementary Table 2 (page 5) FBXW2 F-box and WD-40 domain protein 2 FBXW4 F-box and WD-40 domain protein 4 FGF4 fibroblast growth factor 4 (Kaposi sarcoma oncogene) FOS v-fos FBJ murine osteosarcoma viral oncogene homolog FRAT1 frequently rearranged in advanced T-cell lymphomas FRAT2 frequently rearranged in advanced T-cell lymphomas 2 FZD2 frizzled homolog 2 (Drosophila) GJA1 gap junction protein, alpha 1, 43kDa (connexin 43) GPR135 G protein-coupled receptor 135 GSK3A glycogen synthase kinase 3 alpha HSPG2 proteoglycan 2 () ID2 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein ING1 inhibitor of growth family, member 1 JUN v-jun sarcoma 17 oncogene homolog (avian) JUP junction KREMEN1 kringle containing transmembrane protein 1 KRTHB6 , hair, basic, 6 (monilethrix) LDLR low density lipoprotein receptor (familial hypercholesterolemia) LOC642558 similar to FUS interacting protein (serine-arginine rich) 1 LRP5 low density lipoprotein receptor-related protein 5 LRP6 low density lipoprotein receptor-related protein 6 MAPK9 mitogen-activated protein kinase 9 MAPRE1 microtubule-associated protein, RP/EB family, member 1 MARK4 MAP/microtubule affinity-regulating kinase 4 MYCBP c-myc binding protein NFE2L2 nuclear factor (erythroid-derived 2)-like 2 OVOL1 ovo-like 1(Drosophila) PAFAH1B1 -activating factor acetylhydrolase, isoform Ib, alpha sub.45kDa PLA2G2A phospholipase A2, group IIA (, synovial fluid) PLAU plasminogen activator, PLAUR plasminogen activator, PORCN porcupine homolog (Drosophila) PPARG peroxisome proliferative activated receptor, gamma PPP2CA protein phosphatase 2, catalytic subunit, alpha isoform PPP2R1A protein phosphatase 2, regulatory subunit A (PR 65), alpha isoform PPP2R1B protein phosphatase 2, regulatory subunit A (PR 65), beta isoform PPP2R5C protein phosphatase 2, regulatory subunit B (B56), gamma isoform PPP2R5E protein phosphatase 2, regulatory subunit B (B56), epsilon isoform PRKCA protein kinase C, alpha PRKCG protein kinase C, gamma PRKCI protein kinase C, iota PRKCQ protein kinase C, theta PRKD1 protein kinase D1 PTGS2 prostaglandin-endoperoxide synthase 2 PYGO2 pygopus homolog 2 (Drosophila) RAC1 ras-related C3 botulinum toxin substrate 1 (rho family) RHOV ras homolog gene family, member V RNF4 ring finger protein 4 Supplementary Table 2 (page 6) SEC23B Sec23 homolog B (S. cerevisiae) SEMA3C 3C SENP2 SUMO1/sentrin/SMT3 specific peptidase 2 SMAD2 SMAD, mothers against DPP homolog 2 (Drosophila) SMAD5 SMAD, mothers against DPP homolog 5 (Drosophila) SMAD7 SMAD, mothers against DPP homolog 7 (Drosophila) SMO smoothened homolog (Drosophila) STRA6 stimulated by retinoic acid gene 6 homolog (mouse) T T, homolog (mouse) TCF1 transcription factor 1, hepatic; LF-B1, hepatic nuclear factor (HNF1) TLE2 transducin-like enhancer of split 2 (E(sp1) homolog, Drosophila) TNFSF11 tumor necrosis factor (ligand) superfamily, member 11 TWIST1 twist homolog 1 (acrocephalosyndactyly 3; Saethre-Chotzen synd.) UBXD1 UBX domain containing 1 UBXD2 UBX domain containing 2 UBXD3 UBX domain containing 3 UBXD4 UBX domain containing 4 USP33 ubiquitin specific peptidase 33 VEGF vascular endothelial growth factor VEGFB vascular endothelial growth factor B WNT6 wingless-type MMTV integration site family, member 6 ZNF651 zinc finger protein 651

Not expressed in both normal mucosa and adenomas CDX4 caudal type homeobox transcription factor 4 CSNK1A1 Casein kinase 1, alpha 1 CX40.1 connexin40.1 DKK1 dickkopf homolog 1 (Xenopus laevis) DKK2 dickkopf homolog 2 (Xenopus laevis) DKK4 dickkopf homolog 4 (Xenopus laevis) DKKL1 dickkopf-like 1 (soggy) DLK1 delta-like 1 homolog (Drosophila) DLL3 delta-like 3 (Drosophila) EDN2 EFNA2 ephrin-A2 EFNB3 ephrin-B3 ELAC1 ElaC homolog 1 (E. coli) EN1 homolog 1 EN2 engrailed homolog 2 EPHA6 EPH receptor A6 FGF20 fibroblast growth factor 20 FLJ14712 hypothetical protein FLJ14712 FLJ90166 hypothetical protein FLJ90166 FOSB FBJ murine osteosarcoma viral oncogene homolog B FOXN1 forkhead box N1 FSHB follicle stimulating hormone, beta polypeptide FST follistatin FZD10 frizzled homolog 10 (Drosophila) FZD9 frizzled homolog 9 (Drosophila) Supplementary Table 2 (page 7) GAST GJA10 gap junction protein, alpha 10, 59kDa GJB6 gap junction protein, beta 6 (connexin 30) IGF2 insulin-like growth factor 2 (somatomedin A) IL6 (, beta 2) KREMEN2 kringle containing transmembrane protein 2 KRTAP2-1 keratin associated protein 2-1 LOC391241 similar to Soggy-1 protein precursor (SGY-1) LOC541472 hypothetical LOC541472 LOC641518 hypothetical protein LOC641518 LOC644985 Hypothetical protein LOC644985 MMP26 matrix metallopeptidase 26 NEUROG1 neurogenin 1 NEUROG3 neurogenin 3 NKD1 naked cuticle homolog 1 (Drosophila) NRCAM neuronal cell adhesion molecule PTTG2 pituitary tumor-transforming 2 RUNX2 runt-related transcription factor 2 SFRP4 secreted frizzled-related protein 4 SFRP5 secreted frizzled-related protein 5 SHFM3P1 split hand/foot malformation (ectrodactyly) type 3 pseudogene 1 SIX3 sine oculis homeobox homolog 3 (Drosophila) SOX17 SRY (sex determining region Y)-box 17 SRY (sex determining region Y)-box 2 TLE6 transducin-like enhancer of split 6 (E(sp1) homolog, Drosophila) WIF1 WNT inhibitory factor 1 WISP1 WNT1 inducible signaling pathway protein 1 WISP2 WNT1 inducible signaling pathway protein 2 WISP3 WNT1 inducible signaling pathway protein 3 WNT1 wingless-type MMTV integration site family, member 1 WNT10A wingless-type MMTV integration site family, member 10A WNT10B wingless-type MMTV integration site family, member 10B WNT11 wingless-type MMTV integration site family, member 11 WNT16 wingless-type MMTV integration site family, member 16 WNT3 wingless-type MMTV integration site family, member 3 WNT4 wingless-type MMTV integration site family, member 4 WNT7A wingless-type MMTV integration site family, member 7A WNT7B wingless-type MMTV integration site family, member 7B WNT8A wingless-type MMTV integration site family, member 8A WNT8B wingless-type MMTV integration site family, member 8B WNT9B wingless-type MMTV integration site family, member 9B # Those classified as Wnt-signaling genes by R. Nusse (http://www.stanford.edu/~rnusse/pathways/targets.html and http://www.stanford.edu/~rnusse/pathways/targetcomp.html) and/or in the Gene Ontology database. Genes in red are the Wnt-signaling targets reported in Supplementary Table 5. § Within each category, genes are listed alphabetically by symbol * Significantly overexpressed (Up) or underexpressed (Down) in adenomas (vs. normal mucosa) Supplementary Table 3: A selection of genes whose expression displayed significant positive or negative correlation with adenoma size, i.e., increase or decrease of the mRNA intensity logratio values (adenoma : normal tissue), respectively, from smaller to bigger adenomas *

Positive correlation: Increasing fold changes with increasing adenoma size Affymetrix ID Gene Symbol Gene Name

219189_at FBXL6 F-box and leucine-rich repeat protein 6 235162_at MDM4 Mdm4, transformed 3T3 cell double minute 4, binding protein 32062_at LRRC14 leucine rich repeat containing 14 200821_at LAMP2 lysosomal-associated membrane protein 2 227080_at ZNF697 zinc finger protein 697 206752_s_at DFFB DNA fragmentation factor, 40kDa, beta polypept. (caspase-activated DNase) 226334_s_at AHSA2 AHA1, activator of heat shock 90kDa protein ATPase homolog 2 228150_at LZTR2 transcription regulator 2 203140_at BCL6 B-cell CLL/lymphoma 6 (zinc finger protein 51) 222557_at STMN3 -like 3 226125_at SLC9A3 solute carrier family 9 (sodium/hydrogen exchanger), member 3 201149_s_at TIMP3 TIMP metallopeptidase inhibitor 3 (Sorsby fundus dystrophy) 1557580_at CABIN1 Calcineurin binding protein 1 230097_at GART Phosphoribosylglycinamide formyltransferase 219359_at ATHL1 ATH1, acid -like 1 (yeast) 1555259_at ZAK sterile alpha motif and leucine zipper containing kinase AZK 232201_at NKD2 naked cuticle homolog 2 (Drosophila) 221499_s_at STX16 syntaxin 16 224566_at TncRNA trophoblast-derived noncoding RNA 238449_at LOC440345 hypothetical protein LOC440345 241815_at EST transcribed , hypothetical protein XP_498467 [Homo sapiens] 230494_at EST EST 229390_at RP1-93H18.5 hypothetical protein LOC441168 232052_at LOC440944 hypothetical gene supported by AK128398 1563088_a_at LOC284837 hypothetical protein LOC284837 232052_at LOC440944 Hypothetical gene supported by AK128398

Negative correlation: Decreasing fold changes with increasing adenoma size 216288_at CYSLTR1 cysteinyl leukotriene receptor 1 37226_at BNIP1 BCL2/adenovirus E1B 19kDa interacting protein 1 222377_at TBX10 T-box 10 228962_at PDE4D phosphodiesterase 4D, cAMP-specific 229053_at SYT17 synaptotagmin XVII 230360_at GLDN gliomedin 234709_at CAPN13 calpain 13 239272_at MMP28 matrix metallopeptidase 28 230360_at TMEM61 transmembrane protein 61 223969_s_at RETNLB like beta 212741_at MAOA monoamine oxidase A 240106_at GNPTAB N-acetylglucosamine-1-phosphate , alpha and beta subunits 225822_at TMEM125 transmembrane protein 125 213148_at LOC257407 hypothetical protein LOC257407 229064_s_at EST EST

* These genes were selected from the list of top 500 probes with the highest loading scores along the CCA axis 1 (see Figure 2). Selection criteria were based on the statistical relation between expression change and adenoma size (i.e., how expression change related to adenoma size). Supplementary Table 4. Gene with markedly altered expression in colorectal adenomas (fold-differences of ≥ 4.0 compared with normal mucosa). (Statistical significance was assessed with the Mann-Whitney test using a false discovery rate of 1% as a threshold)

GENES OVEREXPRESSED IN ADENOMAS

Affymetrix ID Fold Difference* Gene Symbol GenBank Gene Name Gene Ontology (Biological Processes) 205513_at 113.4 TCN1 NM_001062 transcobalamin I (vitamin B12 binding protein, R binder family) cobalt ion transport / cobalamin transport 203256_at 81.7 CDH3 NM_001793 cadherin 3, type 1, P-cadherin (placental) cell adhesion / visual perception / response to stimulus 205886_at 75.8 REG1B NM_006507 regenerating islet-derived 1 beta (pancreatic stone protein, pancreatic thread protein) cell proliferation 209792_s_at 60.5 KLK10 BC002710 10 proteolysis / cell cycle / negative regulation of progression through cell cycle 204259_at 56.9 MMP7 NM_002423 matrix metallopeptidase 7 (matrilysin, uterine) metabolism / proteolysis / catabolism 212942_s_at 54.8 KIAA1199 AB033025 KIAA1199 sensory perception of sound 205828_at 33.9 MMP3 NM_002422 matrix metallopeptidase 3 (stromelysin 1, progelatinase) peptidoglycan metabolism / proteolysis / collagen catabolism 241031_at 33.1 NLF1 BE218239 Nuclear localized factor 1 unknown 205983_at 32.7 DPEP1 NM_004413 dipeptidase 1 (renal) proteolysis 205815_at 29.5 REG3A NM_002580 regenerating islet-derived 3 alpha acute-phase response / inflammatory response / heterophilic cell adhesion / development / cell proliferation 232252_at 27.8 DUSP27 AI822125 dual specificity phosphatase 27 (putative) protein amino acid dephosphorylation 206354_at 26.7 SLCO1B3 NM_019844 solute carrier organic anion transporter family, member 1B3 organic anion transport 232370_at 25.3 LOC254057 AI635756 hypothetical protein LOC254057 unknown 207814_at 25.2 DEFA6 NM_001926 , alpha 6, -specific xenobiotic metabolism / response to pest, pathogen or parasite / antimicrobial humoral response / defense response to / defense response to fungi 227475_at 24.4 FOXQ1 AI676059 forkhead box Q1 regulation of transcription, DNA-dependent 205555_s_at 22.2 MSX2 D31771 msh homeobox homolog 2 (Drosophila) skeletal development / regulation of transcription, DNA-dependent 202286_s_at 21.4 TACSTD2 J04152 tumor-associated calcium signal transducer 2 linked / visual perception / cell proliferation / response to stimulus / regulation of progression through cell cycle 1569532_a_at 21.0 UNQ2541 BC035124 MSFL2541 prostaglandin metabolism / transport 210445_at 17.5 FABP6 U19869 fatty acid binding protein 6, ileal (gastrotropin) lipid metabolism / transport / negative regulation of cell proliferation 207607_at 17.3 ASCL2 NM_005170 achaete-scute complex-like 2 (Drosophila) regulation of transcription, DNA-dependent / central nervous system development / peripheral nervous system development / cell differentiation 204268_at 17.1 S100A2 NM_005978 S100 calcium binding protein A2 endothelial cell migration 223509_at 16.1 CLDN2 AF177340 claudin 2 calcium-independent cell-cell adhesion 233413_at 15.3 AU156421 CDNA FLJ13457 fis, clone PLACE1003343 unknown 202859_x_at 14.7 IL8 NM_000584 / cell motility / chemotaxis / cell cycle arrest / G-protein coupled receptor protein signaling pathway / intracellular signaling cascade / cell-cell signaling / negative regulation of cell proliferation / calcium-mediated signaling / regulation of cell adhesion / chemotaxis / neutrophil activation / regulation of retroviral genome replication / response to stimulus / induction of positive chemotaxis / inflammatory response / immune response / signal transduction 238021_s_at 14.2 LOC643911 AA954994 hypothetical protein LOC643911 unknown 204855_at 13.8 SERPINB5 NM_002639 serpin peptidase inhibitor, clade B (ovalbumin), member 5 cell motility 204475_at 13.7 MMP1 NM_002421 matrix metallopeptidase 1 (interstitial collagenase) peptidoglycan metabolism / proteolysis / collagen catabolism 213680_at 13.2 KRT6B AI831452 ectoderm development 209396_s_at 12.7 CHI3L1 M80927 3-like 1 (cartilage -39) metabolism / chitin catabolism 235209_at 11.9 RPESP AW662373 RPE-spondin unknown 207457_s_at 11.2 LY6G6D NM_021246 lymphocyte antigen 6 complex, locus G6D unknown 219955_at 11.0 L1TD1 NM_019079 LINE-1 type transposase domain containing 1 unknown 230615_at 10.9 DUOXA2 AI821606 dual oxidase maturation factor 2 unknown 239579_at 10.6 ABHD7 AI807532 abhydrolase domain containing 7 proteolysis / aromatic compound metabolism 229481_at 10.5 LOC283859 AI990367 hypothetical protein LOC283859 unknown 211122_s_at 10.3 CXCL11 AF002985 (C-X-C motif) ligand 11 chemotaxis / inflammatory response / signal transduction / cell-cell signaling / response to pathogenic fungi / response to stimulus / immune response 205680_at 10.1 MMP10 NM_002425 matrix metallopeptidase 10 (stromelysin 2) peptidoglycan metabolism / proteolysis / collagen catabolism 227702_at 10.0 CYP4X1 AA557324 cytochrome P450, family 4, subfamily X, polypeptide 1 electron transport 207529_at 9.8 DEFA5 NM_021010 defensin, alpha 5, Paneth cell-specific xenobiotic metabolism / response to pest, pathogen or parasite / antimicrobial humoral response / defense response to bacteria / defense response to fungi 220133_at 9.2 APIN NM_017855 APin protein unknown 222549_at 9.0 CLDN1 AF101051 claudin 1 cell adhesion / calcium-independent cell-cell adhesion 236741_at 9.0 WDR72 AW299463 WD repeat domain 72 unknown 205932_s_at 8.5 MSX1 NM_002448 msh homeobox homolog 1 (Drosophila) skeletal development / regulation of transcription, DNA-dependent / organ morphogenesis 209821_at 8.4 C9orf26 AB024518 chromosome 9 open reading frame 26 (NF-HEV) unknown 229638_at 8.4 IRX3 AI681917 iroquois homeobox protein 3 regulation of transcription, DNA-dependent 205044_at 8.4 GABRP NM_014211 gamma-aminobutyric acid (GABA) A receptor, pi ion transport 209752_at 8.2 REG1A AF172331 regenerating islet-derived 1 alpha (pancreatic stone protein, pancreatic thread positive regulation of cell proliferation protein) 210619_s_at 8.2 HYAL1 AF173154 hyaluronoglucosaminidase 1 carbohydrate metabolism 232116_at 7.9 GRHL3 AL137763 grainyhead-like 3 (Drosophila) unknown 203548_s_at 7.8 LPL BF672975 lipoprotein lipase fatty acid metabolism / circulation / lipid catabolism / lipid metabolism 227140_at 7.7 AI343467 CDNA FLJ11041 fis, clone PLACE1004405 unknown 231849_at 7.6 LOC144501 AL162069 hypothetical protein LOC144501 unknown 206574_s_at 7.5 PTP4A3 NM_007079 protein tyrosine phosphatase type IVA, member 3 protein amino acid dephosphorylation 203619_s_at 7.5 FAIM2 NM_012306 Fas apoptotic inhibitory molecule 2 apoptosis 202504_at 7.4 TRIM29 NM_012101 tripartite motif-containing 29 transcription from RNA polymerase II promoter 240045_at 7.4 AI694242 EST unknown 204920_at 7.4 CPS1 AF154830 carbamoyl-phosphate synthetase 1, mitochondrial cycle / arginine biosynthesis / glutamine metabolism / nitrogen compound metabolism / pyrimidine base biosynthesis 204014_at 7.4 DUSP4 NM_001394 dual specificity phosphatase 4 regulation of progression through cell cycle / MAPKKK cascade / protein amino acid dephosphorylation 205470_s_at 7.3 KLK11 NM_006853 kallikrein 11 proteolysis 205595_at 7.3 DSG3 NM_001944 desmoglein 3 (pemphigus vulgaris antigen) cell adhesion 224498_x_at 7.3 AXIN2 BC006295 axin 2 (conductin, axil) signal transduction / frizzled signaling pathway / development / Wnt receptor signaling pathway 206033_s_at 7.2 DSC3 NM_001941 desmocollin 3 cell adhesion 225016_at 7.2 APCDD1 N48299 adenomatosis polyposis coli down-regulated 1 unknown 1560019_at 7.1 DLGAP1 BI869014 Discs, large (Drosophila) homolog-associated protein 1 cell-cell signaling / synaptic transmission 214385_s_at 7.1 MUC5AC AI521646 mucin 5AC, oligomeric mucus/gel-forming cell adhesion / fibril organization and biogenesis 205499_at 7.0 SRPX2 NM_014467 sushi-repeat-containing protein, X-linked 2 unknown 223062_s_at 6.9 PSAT1 BC004863 phosphoserine aminotransferase 1 L-serine biosynthesis / metabolism / pyridoxine biosynthesis 206224_at 6.9 CST1 NM_001898 cystatin SN unknown 219727_at 6.8 DUOX2 NM_014080 dual oxidase 2 electron transport / response to virus / and chemokine mediated signaling pathway / cuticle biosynthesis / hormone biosynthesis / superoxide release / hydrogen peroxide catabolism / hydrogen peroxide biosynthesis / response to cAMP 210147_at 6.8 ART3 U47054 ADP-ribosyltransferase 3 protein amino acid ADP-ribosylation 1554436_a_at 6.8 REG4 AY126671 regenerating islet-derived family, member 4 unknown 236894_at 6.7 AI203404 EST unknown 218963_s_at 6.6 KRT23 NM_015515 keratin 23 ( inducible) unknown 207850_at 6.6 CXCL3 NM_002090 chemokine (C-X-C motif) ligand 3 chemotaxis / inflammatory response / G-protein coupled receptor protein signaling pathway / response to stimulus / immune response Supplementary Table 4, page 2 204470_at 6.6 CXCL1 NM_001511 chemokine (C-X-C motif) ligand 1 ( growth stimulating activity, alpha) chemotaxis / inflammatory response / G-protein coupled receptor protein signaling pathway / intracellular signaling cascade / nervous system development / negative regulation of cell proliferation / cytoskeleton organization and biogenesis / immune response / signal transduction 229613_at 6.5 BF724178 Weakly similar to naked cuticle homolog 1; naked cuticle-1; Dvl-binding protein [Pan unknown troglodytes] 1568603_at 6.4 CADPS AI912173 Ca2+-dependent secretion activator exocytosis / protein transport 202376_at 6.4 SERPINA3 NM_001085 serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 acute-phase response / inflammatory response / regulation of lipid metabolism 226034_at 6.2 BE222344 Homo sapiens, clone IMAGE:3881549, mRNA unknown 218000_s_at 6.0 PHLDA1 NM_007350 pleckstrin homology-like domain, family A, member 1 apoptosis 1561330_at 5.9 DSG4 BC039098 desmoglein 4 cell adhesion 207033_at 5.9 GIF NM_005142 gastric (vitamin B synthesis) cobalt ion transport 227051_at 5.8 AU157716 Homo sapiens, clone IMAGE:4393354, mRNA unknown 213880_at 5.8 LGR5 AL524520 leucine-rich repeat-containing G protein-coupled receptor 5 signal transduction / G-protein coupled receptor protein signaling pathway 228754_at 5.8 SLC6A6 BG150485 solute carrier family 6 (neurotransmitter transporter, taurine), member 6 amino acid metabolism / neurotransmitter transport 232203_at 5.7 AA554714 CDNA FLJ13722 fis, clone PLACE2000455 unknown 212531_at 5.7 LCN2 NM_005564 lipocalin 2 (oncogene 24p3) transport 228303_at 5.6 AW014155 Similar to UDP-N-acetyl-alpha-D-galactosamine:polypeptide N- unknown acetylgalactosaminyltransferase 6 (GalNAc-T6) 219956_at 5.6 GALNT6 NM_007210 UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase protein amino acid O-linked glycosylation 211207_s_at 5.6 ACSL6 AF129166 acyl-CoA6 (GalNAc-T6) synthetase long-chain family member 6 lipid metabolism / acyl-CoA metabolism / fatty acid metabolism 216325_x_at 5.6 RTEL1 AF217796 regulator of telomere elongation helicase 1 nucleobase, nucleoside, nucleotide and nucleic acid metabolism 228955_at 5.6 AL041761 Weakly similar to NP_990560.1 very low density lipoprotein (VLDL)/vitellogenin unknown receptor [Gallus gallus] 205825_at 5.5 PCSK1 NM_000439 proprotein convertase subtilisin/kexin type 1 proteolysis / cell-cell signaling / metabolism 225541_at 5.5 RPL22L1 BE274422 ribosomal protein L22-like 1 protein biosynthesis / electron transport 215185_at 5.5 AK024177 Homo sapiens, clone IMAGE:3851018, mRNA unknown 1554576_a_at 5.4 ETV4 BC007242 ets variant gene 4 (E1A enhancer binding protein, E1AF) regulation of transcription, DNA-dependent 236918_s_at 5.4 LRRC34 AW975772 leucine rich repeat containing 34 unknown 206172_at 5.4 IL13RA2 NM_000640 receptor, alpha 2 unknown 220003_at 5.3 LRRC36 NM_018296 leucine rich repeat containing 36 unknown 220658_s_at 5.3 ARNTL2 NM_020183 aryl hydrocarbon receptor nuclear translocator-like 2 regulation of transcription, DNA-dependent / signal transduction // entrainment of circadian / regulation of transcription from RNA polymerase II promoter / 205174_s_at 5.3 QPCT NM_012413 glutaminyl-peptide cyclotransferase (glutaminyl cyclase) proteincircadian modification rhythm / proteolysis 223694_at 5.3 TRIM7 AF220032 tripartite motif-containing 7 unknown 204281_at 5.2 TEAD4 NM_003213 TEA domain family member 4 skeletal development / regulation of transcription, DNA-dependent / regulation of transcription from RNA polymerase II promoter / muscle development 205421_at 5.2 SLC22A3 NM_021977 solute carrier family 22 (extraneuronal monoamine transporter), member 3 organic cation transport 232654_s_at 5.2 UGT1A6 BE873420 UDP 1 family, polypeptide A6 xenobiotic metabolism 201506_at 5.2 TGFBI NM_000358 transforming growth factor, beta-induced, 68kDa cell adhesion / visual perception / cell proliferation / response to stimulus 235845_at 5.2 SP5 AI380207 Sp5 transcription factor regulation of transcription, DNA-dependent 244612_at 5.2 AW117181 EST unknown 1568639_a_at 5.1 BC033667 Homo sapiens, clone IMAGE:5110701, mRNA unknown 228649_at 5.1 NOTUM AL574571 notum pectinacetylesterase homolog (Drosophila) unknown 205234_at 5.0 SLC16A4 NM_004696 solute carrier family 16 (monocarboxylic acid transporters), member 4 monocarboxylic acid transport 209774_x_at 5.0 CXCL2 M57731 chemokine (C-X-C motif) ligand 2 chemotaxis / inflammatory response / G-protein coupled receptor protein signaling pathway / response to stimulus 208209_s_at 4.8 C4BPB NM_000716 complement component 4 binding protein, beta complement activation, classical pathway / / innate immune response 202718_at 4.8 IGFBP2 NM_000597 insulin-like growth factor binding protein 2, 36kDa regulation of cell growth 230398_at 4.8 TNS4 AA158731 tensin 4 intracellular signaling cascade 230746_s_at 4.7 STC1 AW003173 Stanniocalcin 1 calcium ion homeostasis / cell surface receptor linked signal transduction / cell- cell signaling / response to nutrient 216255_s_at 4.7 GRM8 AC000099 glutamate receptor, metabotropic 8 signal transduction / G-protein coupled receptor protein signaling pathway / negative regulation of adenylate cyclase activity / synaptic transmission / visual perception / sensory perception of smell / response to stimulus 206286_s_at 4.7 TDGF1 NM_003212 teratocarcinoma-derived growth factor 1 activation of MAPK activity / morphogenesis of a branching structure / epidermal growth factor receptor signaling pathway / development / positive regulation of cell proliferation / determination of anterior/posterior axis, embryo / regulation of signal transduction / peptidyl-serine phosphorylation / cell differentiation / positive regulation of cell migration / mammary gland development / negative regulation of apoptosis / positive regulation of peptidyl- / mesodermal cell fate determination 204885_s_at 4.7 MSLN NM_005823 mesothelin cell adhesion 206023_at 4.7 NMU NM_006681 regulation of smooth muscle contraction / signal transduction / neuropeptide signaling pathway / digestion / G-protein coupled receptor protein signaling pathway 226446_at 4.6 HES6 AW249678 hairy and enhancer of split 6 (Drosophila) regulation of transcription, DNA-dependent / cell differentiation / development 209309_at 4.6 AZGP1 D90427 alpha-2-glycoprotein 1, zinc cell adhesion / negative regulation of cell proliferation / lipid catabolism / antigen presentation / cell communication 229576_s_at 4.6 TBX3 N29712 T-box 3 (ulnar mammary syndrome) skeletal development / regulation of transcription from RNA polymerase II promoter / morphogenesis / regulation of transcription, DNA-dependent 219270_at 4.5 CHAC1 NM_024111 ChaC, cation transport regulator-like 1 (E. coli) unknown 206467_x_at 4.5 TNFRSF6B NM_003823 tumor necrosis factor receptor superfamily, member 6b, decoy nucleobase, nucleoside, nucleotide and nucleic acid metabolism / apoptosis 204351_at 4.5 S100P NM_005980 S100 calcium binding protein P endothelial cell migration 206390_x_at 4.4 PF4 NM_002619 (chemokine (C-X-C motif) ligand 4) immune response / negative regulation of angiogenesis / cytokine and chemokine mediated signaling pathway / platelet activation / immune cell chemotaxis / negative regulation of megakaryocyte differentiation / response to stimulus / chemotaxis 225806_at 4.4 JUB AI289311 jub, ajuba homolog (Xenopus laevis) unknown 209773_s_at 4.4 RRM2 BC001886 ribonucleotide reductase M2 polypeptide DNA replication / deoxyribonucleoside diphosphate metabolism 235153_at 4.4 RNF183 BE796148 ring finger protein 183 unknown 212014_x_at 4.4 CD44 AI493245 CD44 molecule (Indian blood group) cell adhesion 1555731_a_at 4.4 AP1S3 AF393369 adaptor-related protein complex 1, sigma 3 subunit intracellular protein transport / endocytosis / vesicle-mediated transport 201195_s_at 4.3 SLC7A5 AB018009 solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 amino acid metabolism / amino acid transport 236471_at 4.3 NFE2L3 AI949827 nuclear factor (erythroid-derived 2)-like 3 regulation of transcription, DNA-dependent / transcription from RNA polymerase II promoter 223974_at 4.3 MGC11082 BC005130 hypothetical protein MGC11082 unknown 219710_at 4.3 SH3TC2 NM_024577 SH3 domain and tetratricopeptide repeats 2 unknown 201467_s_at 4.2 NQO1 AI039874 NAD(P)H dehydrogenase, quinone 1 electron transport / xenobiotic metabolism / nitric oxide biosynthesis / synaptic transmission, cholinergic / response to toxin 205476_at 4.2 CCL20 NM_004591 chemokine (C-C motif) ligand 20 chemotaxis / inflammatory response / signal transduction / cell-cell signaling / antimicrobial humoral response / defense response to bacteria / response to stimulus / chemotaxis / immune response 227919_at 4.2 UCA1 AA702248 UCA1 protein unknown 202917_s_at 4.2 S100A8 NM_002964 S100 calcium binding protein A8 (calgranulin A) inflammatory response 222830_at 4.2 GRHL1 BE566136 grainyhead-like 1 (Drosophila) unknown 208250_s_at 4.2 DMBT1 NM_004406 deleted in malignant brain tumors 1 cell cycle / epithelial cell differentiation / induction of bacterial agglutination / innate immune response / negative regulation of progression through cell cycle 230964_at 4.1 FREM2 N66307 FRAS1 related extracellular matrix protein 2 cell communication / cell adhesion / development 210021_s_at 4.1 UNG2 BC004877 uracil-DNA 2 regulation of progression through cell cycle / carbohydrate metabolism / base- excision repair / DNA repair / response to DNA damage stimulus 205240_at 4.1 GPSM2 NM_013296 G-protein signalling modulator 2 (AGS3-like, C. elegans) signal transduction / G-protein coupled receptor protein signaling pathway 225767_at 4.1 AI825833 EST, weakly similar to PIHUB6 salivary proline-rich protein precursor PRB1 unknown 211163_s_at 4.1 TNFRSF10C AF012536 (H.sapiens)tumor necrosis factor receptor superfamily, member 10c, decoy without an apoptosis / signal transduction intracellular domain Supplementary Table 4, page 3 200660_at 4.1 S100A11 NM_005620 S100 calcium binding protein A11 (calgizzarin) signal transduction / negative regulation of DNA replication / negative regulation of cell proliferation 222608_s_at 4.1 ANLN AK023208 anillin, actin binding protein (scraps homolog, Drosophila) cytokinesis 203722_at 4.1 ALDH4A1 NM_003748 aldehyde dehydrogenase 4 family, member A1 proline biosynthesis / proline catabolism / proline metabolism 203798_s_at 4.1 VSNL1 NM_003385 visinin-like 1 unknown 226064_s_at 4.0 DGAT2 AW469523 diacylglycerol O- homolog 2 (mouse) triacylglycerol biosynthesis 219795_at 4.0 SLC6A14 NM_007231 solute carrier family 6 (amino acid transporter), member 14 amino acid metabolism / neurotransmitter transport / amino acid transport

GENES UNDEREXPRESSED IN ADENOMAS

Affy metrix ID Fold Difference* Gene Symbol GenBank Gene Name Gene Ontology (Biological Processes) 207080_s_at 74.1 PYY NM_004160 peptide YY cell motility / cytoskeleton organization and biogenesis / G-protein coupled receptor protein signaling pathway / cell-cell signaling / digestion / feeding behavior / cell proliferation 206422_at 68.5 GCG NM_002054 glucagon signal transduction / G-protein coupled receptor protein signaling pathway / feeding behavior / cell proliferation 213921_at 61.3 SST NM_001048 unknown 221091_at 60.2 INSL5 NM_005478 insulin-like 5 physiological process 207502_at 54.6 GUCA2B NM_007102 guanylate cyclase activator 2B (uroguanylin) excretion 206784_at 53.8 AQP8 NM_001169 aquaporin 8 water transport 229152_at 42.7 C4orf7 AI718421 open reading frame 7 unknown 205242_at 41.7 CXCL13 NM_006419 chemokine (C-X-C motif) ligand 13 (B-cell chemoattractant) chemotaxis / inflammatory response / elevation of cytosolic calcium ion concentration / cell-cell signaling / response to stimulus / immune response 214601_at 37.7 TPH1 AI350339 hydroxylase 1 (tryptophan 5-monooxygenase) serotonin biosynthesis from tryptophan / aromatic amino acid family metabolism / tryptophan metabolism 240157_at 36.1 SLC30A10 AV694053 Solute carrier family 30, member 10 cation transport 207003_at 30.7 GUCA1B NM_002098 guanylate cyclase activator 2A (guanylin) signal transduction 204697_s_at 29.2 CHGA NM_001275 chromogranin A (parathyroid secretory protein 1) blood pressure regulation 224412_s_at 28.4 TRPM6 AF350881 transient receptor potential cation channel, subfamily M, member 6 protein amino acid phosphorylation / calcium ion transport 214598_at 25.8 CLDN8 AL049977 claudin 8 calcium-independent cell-cell adhesion 231773_at 24.9 ANGPTL1 BF002046 angiopoietin-like 1 unknown 204719_at 23.5 ABCA8 NM_007168 ATP-binding cassette, sub-family A (ABC1), member 8 transport 1552296_at 23.2 VMD2L2 NM_153274 vitelliform macular dystrophy 2-like 2 ion transport 219669_at 22.9 CD177 NM_020406 CD177 molecule unknown 230788_at 21.4 GCNT2 BF059748 glucosaminyl (N-acetyl) transferase 2, I-branching enzyme (I blood group) glycosaminoglycan biosynthesis / protein amino acid O-linked glycosylation / development 220834_at 20.3 MS4A12 NM_017716 membrane-spanning 4-domains, subfamily A, member 12 signal transduction 222722_at 20.2 OGN AV700059 (osteoinductive factor, mimecan) unknown 209735_at 19.9 ABCG2 AF098951 ATP-binding cassette, sub-family G (WHITE), member 2 transport / response to drug 205950_s_at 19.8 CA1 NM_001738 carbonic anhydrase I one-carbon compound metabolism 220136_s_at 19.1 CRYBA2 NM_005209 crystallin, beta A2 unknown 210548_at 18.8 CCL23 U58913 chemokine (C-C motif) ligand 23 calcium ion homeostasis / chemotaxis / inflammatory response / signal 204606_at 18.7 CCL21 NM_002989 chemokine (C-C motif) ligand 21 transductionchemotaxis / /inflammatory G-protein coupled response receptor / immune protein response signaling / signal pathway transduction / cell-cell / cell-cell signaling / response to stimulus 228592_at 18.7 MS4A1 AW474852 membrane-spanning 4-domains, subfamily A, member 1 immune response / signal transduction / activation 209612_s_at 18.4 ADH1B M24317 alcohol dehydrogenase IB (class I), beta polypeptide ethanol oxidation 220794_at 18.3 GREM2 NM_022469 gremlin 2, cysteine knot superfamily, homolog (Xenopus laevis) unknown 207140_at 18.3 ALPI NM_001631 alkaline phosphatase, intestinal metabolism / phosphorylation 205544_s_at 18.3 CR2 NM_001877 complement component (3d/Epstein Barr virus) receptor 2 complement activation, classical pathway / innate immune response 217562_at 18.2 FAM5C BF589529 family with sequence similarity 5, member C unknown 210072_at 18.1 CCL19 U88321 chemokine (C-C motif) ligand 19 calcium ion homeostasis / chemotaxis / inflammatory response / signal transduction / response to virus / response to stimulus / immune response / cell communication 206209_s_at 17.9 CA4 NM_000717 carbonic anhydrase IV one-carbon compound metabolism / visual perception / response to stimulus 229230_at 17.2 OSTalpha AA702685 organic solute transporter alpha unknown 205697_at 16.8 SCGN NM_006998 secretagogin, EF-hand calcium binding protein unknown 208383_s_at 16.4 PCK1 NM_002591 phosphoenolpyruvate carboxykinase 1 (soluble) gluconeogenesis 1555231_a_at 16.2 C21orf88 AF426267 chromosome 21 open reading frame 88 unknown 223623_at 15.9 ECRG4 AF325503 esophageal related gene 4 protein unknown 206577_at 15.9 VIP NM_003381 vasoactive intestinal peptide muscle contraction / G-protein coupled receptor protein signaling pathway / cell- cell signaling / fluid secretion / positive regulation of cell proliferation 213764_s_at 15.9 MFAP5 AW665892 microfibrillar associated protein 5 unknown 222943_at 15.7 GBA3 AW235567 glucosidase, beta, acid 3 (cytosolic) carbohydrate metabolism 205433_at 15.7 BCHE NM_000055 butyrylcholinesterase cocaine metabolism 230269_at 15.4 B3GALT5 AI963605 UDP-Gal:betaGlcNAc beta 1,3-, polypeptide 5 protein amino acid glycosylation 207260_at 15.1 FEV NM_017521 FEV (ETS oncogene family) regulation of transcription, DNA-dependent / transcription from RNA polymerase II promoter 1559884_at 15.0 BC038540 Homo sapiens, clone IMAGE:5187335, mRNA unknown 207504_at 14.9 CA7 NM_005182 carbonic anhydrase VII one-carbon compound metabolism 236313_at 14.9 CDKN2B AW444761 cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) regulation of cyclin dependent protein kinase activity / cell cycle arrest/ negative regulation of cell proliferation / negative regulation of progression through cell cycle 210198_s_at 13.7 PLP1 BC002665 proteolipid protein 1 (Pelizaeus-Merzbacher disease, spastic paraplegia 2, unknown uncomplicated) 1563692_at 13.2 AK025044 CDNA: FLJ21391 fis, clone COL03479 unknown 205861_at 13.2 SPIB NM_003121 Spi-B transcription factor (Spi-1/PU.1 related) regulation of transcription from RNA polymerase II promoter / regulation of transcription, DNA-dependent 205464_at 12.9 SCNN1B NM_000336 sodium channel, nonvoltage-gated 1, beta (Liddle syndrome) sodium ion transport / excretion / response to stimulus 206502_s_at 12.4 INSM1 NM_002196 insulinoma-associated 1 regulation of transcription, DNA-dependent / transcription from RNA polymerase II promoter 228504_at 12.3 AI828648 Strongly similar to NP_002967.1 sodium channel, voltage-gated, type VII, alpha unknown 238177_at 12.1 SLC6A19 AA873542 [HomoSolute carriersapiens] family 6 (neutral amino acid transporter), member 19 neurotransmitter transport / amino acid transport 204260_at 12.0 CHGB NM_001819 chromogranin B (secretogranin 1) unknown 206134_at 12.0 ADAMDEC1 NM_014479 ADAM-like, decysin 1 proteolysis / negative regulation of cell adhesion / -mediated signaling pathway 215563_s_at 11.8 MSTP9 U28055 stimulating, pseudogene 9 proteolysis 213071_at 11.8 DPT AL049798 dermatopontin cell adhesion 215657_at 11.7 SLC26A3 AK025044 Solute carrier family 26, member 3 anion transport / excretion / sulfate transport 209167_at 11.5 GPM6B AI419030 glycoprotein M6B nervous system development / cell differentiation / nervous system development 209687_at 11.3 CXCL12 U19495 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1) calcium ion homeostasis / chemotaxis / inflammatory response / immune 206294_at 11.3 HSD3B2 NM_000198 hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta- 2 responseC21-steroid / cell hormone adhesion biosynthesis / signal transduction / androgen / biosynthesisG-protein coupled / receptor protein biosynthesis 204035_at 11.2 SCG2 NM_003469 secretogranin II (chromogranin C) protein secretion 232245_at 11.1 SLC25A34 AU151211 solute carrier family 25, member 34 transport 208399_s_at 11.1 EDN3 NM_000114 signal transduction / cell-cell signaling / sensory perception of sound / pathogenesis / morphogenesis / regulation of vasoconstriction / regulation of blood vessel size / development / circulation 212713_at 10.9 MFAP4 R72286 microfibrillar-associated protein 4 cell adhesion 220026_at 10.8 CLCA4 NM_012128 chloride channel, calcium activated, family member 4 chloride transport 206282_at 10.6 NEUROD1 NM_002500 neurogenic differentiation 1 regulation of transcription, DNA-dependent / nervous system development / cell differentiation 209763_at 10.6 CHRDL1 AL049176 chordin-like 1 development 228854_at 10.6 AI492388 EST unknown 210738_s_at 10.6 SLC4A4 AF011390 solute carrier family 4, sodium bicarbonate cotransporter, member 4 sodium ion transport Supplementary Table 4, page 4 227826_s_at 10.4 SORBS2 AW138143 Sorbin and SH3 domain containing 2 transport 207895_at 10.4 NAALADL1 NM_005468 N-acetylated alpha-linked acidic dipeptidase-like 1 proteolysis 228885_at 10.3 MAMDC2 AI862120 MAM domain containing 2 unknown 203980_at 10.1 FABP4 NM_001442 fatty acid binding protein 4, adipocyte transport 202920_at 9.8 ANK2 BF726212 2, neuronal signal transduction / metabolism 205509_at 9.6 CPB1 NM_001871 carboxypeptidase B1 (tissue) proteolysis 206070_s_at 9.5 EPHA3 AF213459 EPH receptor A3 protein amino acid phosphorylation / signal transduction / transmembrane receptor protein tyrosine kinase signaling pathway 1558324_a_at 9.4 BC029135 Homo sapiens, clone IMAGE:5189562, mRNA unknown 206869_at 9.3 CHAD NM_001267 chondroadherin regulation of cell growth 217546_at 9.3 MT1K R06655 metallothionein 1M unknown 204846_at 8.9 CP NM_000096 ceruloplasmin (ferroxidase) copper ion transport / copper ion homeostasis / iron ion homeostasis 206084_at 8.9 PTPRR NM_002849 protein tyrosine phosphatase, receptor type, R / protein amino acid dephosphorylation // traceable author statement /// 6470 // protein amino acid dephosphorylation // inferred from electronic annotation 230360_at 8.7 GLDN AW006648 gliomedin phosphate transport 206898_at 8.3 CDH19 NM_021153 cadherin 19, type 2 cell adhesion 206198_s_at 8.3 CEACAM7 L31792 -related cell adhesion molecule 7 unknown 228186_s_at 8.3 RSPO3 BF589322 R-spondin 3 homolog (Xenopus laevis) electron transport 202994_s_at 8.1 FBLN1 Z95331 fibulin 1 chitin metabolism 225575_at 8.1 LIFR AI680541 leukemia inhibitory factor receptor alpha cell surface receptor linked signal transduction 228706_s_at 8.0 CLDN23 BF110053 claudin 23 calcium-independent cell-cell adhesion 202888_s_at 7.9 ANPEP NM_001150 alanyl aminopeptidase (aminopeptidase N, aminopeptidase M, microsomal angiogenesis / proteolysis / cell differentiation / development 220291_at 7.9 GDPD2 NM_017711 aminopeptidase,glycerophosphodiester CD13, phosphodiesterase p150) domain containing 2 glycerol metabolism 208450_at 7.8 LGALS2 NM_006498 , galactoside-binding, soluble, 2 ( 2) /// lectin, galactoside-binding, unknown soluble, 2 (galectin 2) 235004_at 7.7 RBM24 AI677701 RNA binding motif protein 24 unknown 219728_at 7.6 MYOT NM_006790 myotilin muscle contraction 202037_s_at 7.6 SFRP1 NM_003012 secreted frizzled-related protein 1 Wnt receptor signaling pathway / cell differentiation / development 210571_s_at 7.5 CMAH AF074480 cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMP-N- unknown acetylneuraminate monooxygenase) 205384_at 7.5 FXYD1 NM_005031 FXYD domain containing ion transport regulator 1 (phospholemman) on transport / chloride transport / muscle contraction 227061_at 7.5 AI088063 CDNA FLJ44429 fis, clone UTERU2015653 unknown 203305_at 7.4 F13A1 NM_000129 coagulation factor XIII, A1 polypeptide blood coagulation / peptide cross-linking 207392_x_at 7.4 UGT2B15 NM_001076 UDP glucuronosyltransferase 2 family, polypeptide B15 xenobiotic metabolism / steroid metabolism 206189_at 7.4 UNC5C NM_003728 unc-5 homolog C (C. elegans) apoptosis / signal transduction / guidance / brain development 205154_at 7.3 LRRN5 NM_006338 leucine rich repeat neuronal 5 cell adhesion / signal transduction 234092_s_at 7.2 TM6SF2 AF255923 transmembrane 6 superfamily member 2 unknown 232739_at 7.2 AK025419 CDNA: FLJ21766 fis, clone COLF7179 unknown 230830_at 7.2 OSTbeta AI479168 organic solute transporter beta unknown 1559477_s_at 7.1 MEIS1 AL832770 Meis1, myeloid ecotropic viral integration site 1 homolog (mouse) regulation of transcription, DNA-dependent / development 228547_at 7.1 NRXN1 BF509242 neurexin 1 cell adhesion / axon guidance 203130_s_at 7.0 KIF5C NM_004522 family member 5C organelle organization and biogenesis / microtubule-based movement 206149_at 7.0 LOC63928 NM_022097 hepatocellular carcinoma antigen gene 520 unknown 1554530_at 7.0 MGC33530 BC028404 hypothetical protein MGC33530 unknown 207051_at 7.0 SLC17A4 NM_005495 solute carrier family 17 (sodium phosphate), member 4 phosphate metabolism / sodium ion transport 235400_at 7.0 FCRLM1 AL560266 Fc receptor-like and mucin-like 1 unknown 1564154_at 6.9 BC041466 Homo sapiens, clone IMAGE:5213841, mRNA unknown 215118_s_at 6.8 IGHG1 AW519168 Immunoglobulin heavy constant gamma 1 (G1m marker) immune response / antigen presentation, endogenous antigen / antigen processing, endogenous antigen via MHC class I / cellular defense response 209301_at 6.8 CA2 M36532 carbonic anhydrase II one-carbon compound metabolism 227282_at 6.8 PCDH19 AB037734 protocadherin 19 cell adhesion 219087_at 6.8 ASPN NM_017680 asporin (LRR class 1) unknown 203951_at 6.8 CNN1 NM_001299 calponin 1, basic, smooth muscle regulation of smooth muscle contraction / actomyosin structure organization and 238143_at 6.8 LOC646627 AW001557 hypothetical protein LOC646627 unknownbiogenesis 205380_at 6.8 PDZK1 NM_002614 PDZ domain containing 1 unknown 206664_at 6.7 SI NM_001041 -isomaltase (alpha-glucosidase) carbohydrate metabolism 208367_x_at 6.7 CYP3A4 NM_000776 cytochrome P450, family 3, subfamily A, polypeptide 4 electron transport / lipid metabolism / xenobiotic metabolism 242372_s_at 6.7 MFSD4 AL542291 major facilitator superfamily domain containing 4 unknown 224963_at 6.7 SLC26A2 AK025078 solute carrier family 26 (sulfate transporter), member 2 sulfate transport 236351_at 6.6 LOC389023 AI499651 hypothetical gene supported by BC032913; BC048425 unknown 227419_x_at 6.6 PLAC9 AW964972 placenta-specific 9 unknown 206950_at 6.6 SCN9A NM_002977 sodium channel, voltage-gated, type IX, alpha sodium ion transport 201497_x_at 6.5 MYH11 NM_022844 , heavy polypeptide 11, smooth muscle striated muscle contraction / regulation of progression through cell cycle / cell proliferation / skeletal development / imprinting / signaling pathway 221259_s_at 6.5 TEX11 NM_031276 testis expressed sequence 11 /// testis expressed sequence 11 unknown 237802_at 6.5 XKR4 R54212 XK, Kell blood group complex subunit-related family, member 4 unknown 204192_at 6.4 CD37 NM_001774 CD37 molecule protein amino acid N-linked glycosylation 226492_at 6.3 SEMA6D AL036088 sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) nervous system development / cell differentiation 6D 203296_s_at 6.2 ATP1A2 NM_000702 ATPase, Na+/K+ transporting, alpha 2 (+) polypeptide potassium ion transport / sodium ion transport / metabolism / monovalent inorganic cation transport / ATP hydrolysis coupled proton transport / sperm motility / hydrogen ion homeostasis 228640_at 6.2 BE644809 CDNA clone IMAGE:4800096 unknown 234994_at 6.2 KIAA1913 AA088177 KIAA1913 unknown 228195_at 6.2 MGC13057 BE645119 Hypothetical protein MGC13057 unknown 242733_at 6.1 HPGD AI457588 Hydroxyprostaglandin dehydrogenase 15-(NAD) lipid metabolism / fatty acid metabolism / prostaglandin metabolism / transforming

growth factor beta receptor signaling pathway / pregnancy / parturition / lipoxygenase pathway / negative regulation of progression through cell cycle 225458_at 6.1 LOC25845 BF528646 hypothetical LOC25845 unknown 213407_at 6.0 PHLPPL AB023148 PH domain and leucine rich repeat protein phosphatase-like unknown 241436_at 6.0 SCNN1G AI985987 sodium channel, nonvoltage-gated 1, gamma sodium ion transport / excretion / response to stimulus 228750_at 6.0 COL14A1 AI693516 Collagen, type XIV, alpha 1 (undulin) phosphate transport / cell adhesion / collagen fibril organization / extracellular matrix organization and biogenesis 221933_at 6.0 NLGN4X AI338338 neuroligin 4, X-linked cell adhesion 227198_at 6.0 AFF3 AW085505 AF4/FMR2 family, member 3 regulation of transcription, DNA-dependent / development 220059_at 6.0 BRDG1 NM_012108 BCR downstream signaling 1 intracellular protein transport / membrane fusion / humoral immune response / intracellular signaling cascade / signal transduction 1564323_at 6.0 AK025042 CDNA: FLJ21389 fis, clone COL03455 unknown 232431_at 5.9 NR3C1 AI934556 subfamily 3, group C, member 1 () regulation of transcription, DNA-dependent / transcription from RNA polymerase II promoter / inflammatory response / signal transduction / sex determination 211766_s_at 5.9 PNLIPRP2 BC005989 pancreatic lipase-related protein 2 /// pancreatic lipase-related protein 2 triacylglycerol metabolism / lipid catabolism / lipid metabolism 235849_at 5.9 SCARA5 BE787752 scavenger receptor class A, member 5 (putative) phosphate transport 219519_s_at 5.9 SIGLEC1 NM_023068 sialic acid binding Ig-like lectin 1, /// sialic acid binding Ig-like lectin 1, inflammatory response / cell-matrix adhesion / cell-cell adhesion sialoadhesin 229313_at 5.9 AA843962 ESTs unknown 213800_at 5.9 CFH X04697 complement complement activation, alternative pathway / innate immune response 230895_at 5.9 CRTL1 AI760252 EST unknown 233180_at 5.9 RNF152 AU147152 Ring finger protein 152 ubiquitin cycle 209660_at 5.8 TTR AF162690 transthyretin (prealbumin, amyloidosis type I) thyroid hormone generation / transport 219059_s_at 5.8 XLKD1 AL574194 extracellular link domain containing 1 cell motility / cell-matrix adhesion / response to wounding / morphogenesis 207766_at 5.8 CDKL1 NM_004196 cyclin-dependent kinase-like 1 (CDC2-related kinase) regulation of progression through cell cycle / protein amino acid phosphorylation 244370_at 5.8 KIAA2022 AI743137 KIAA2022 protein unknown 221122_at 5.7 HRASLS2 NM_017878 HRAS-like suppressor 2 unknown Supplementary Table 4, page 5 224836_at 5.7 TP53INP2 AL109824 tumor protein p53 inducible nuclear protein 2 unknown 206100_at 5.7 CPM NM_001874 carboxypeptidase M proteolysis / aromatic compound metabolism / morphogenesis 205524_s_at 5.7 HAPLN1 NM_001884 hyaluronan and proteoglycan link protein 1 cell adhesion 207251_at 5.7 MEP1B NM_005925 meprin A, beta proteolysis / digestion 202242_at 5.7 TM4SF2 NM_004615 7 protein amino acid N-linked glycosylation 214142_at 5.7 ZG16 AI732905 granule protein 16 unknown 230204_at 5.6 AU144114 cartilage linking protein 1 unknown 228143_at 5.6 AI684991 Homo sapiens cDNA: FLJ22704 fis, clone HSI12602 unknown 208343_s_at 5.6 NR5A2 AF146343 nuclear receptor subfamily 5, group A, member 2 regulation of transcription, DNA-dependent / transcription from RNA polymerase II promoter / morphogenesis / embryonic development / homeostasis 224411_at 5.6 PLA2G12B AF349540 phospholipase A2, group XIIB /// phospholipase A2, group XIIB lipid catabolism 216333_x_at 5.6 TNXB M25813 tenascin XB cell-matrix adhesion 206121_at 5.5 AMPD1 NM_000036 adenosine monophosphate deaminase 1 (isoform M) purine ribonucleoside monophosphate biosynthesis 228365_at 5.5 CPNE8 AI765180 copine VIII unknown 234563_at 5.5 PDE3A AK000795 Phosphodiesterase 3A, cGMP-inhibited lipid metabolism / signal transduction 225275_at 5.5 EDIL3 AA053711 EGF-like repeats and discoidin I-like domains 3 cell adhesion / development 236121_at 5.5 OR51E2 AI805082 olfactory receptor, family 51, subfamily E, member 2 signal transduction / G-protein coupled receptor protein signaling pathway / sensory perception of smell / response to stimulus 205185_at 5.5 SPINK5 NM_006846 serine peptidase inhibitor, Kazal type 5 negative regulation of angiogenesis / antimicrobial humoral response / extracellular matrix organization and biogenesis / anti-inflammatory response / epithelial cell differentiation / hair cell differentiation / anagen / regulation of differentiation / negative regulation of immune response / epidermal cell differentiation 206030_at 5.4 ASPA NM_000049 (Canavan disease) aspartate catabolism 214038_at 5.4 CCL8 AI984980 chemokine (C-C motif) ligand 8 calcium ion transport / exocytosis / chemotaxis / inflammatory response / signal transduction / cell-cell signaling / response to virus / response to stimulus / immune response 221602_s_at 5.4 FAIM3 AF057557 Fas apoptotic inhibitory molecule 3 anti-apoptosis / cellular defense response 206484_s_at 5.4 XPNPEP2 NM_003399 X-prolyl aminopeptidase (aminopeptidase P) 2, membrane-bound proteolysis 209074_s_at 5.4 FAM107A AL050264 family with sequence similarity 107, member A regulation of cell growth 205498_at 5.4 GHR NM_000163 receptor skeletal development / endocytosis / growth 208244_at 5.3 BMP3 NM_001201 bone morphogenetic protein 3 (osteogenic) ossification / cell-cell signaling / cell differentiation / cartilage development / 228598_at 5.3 DPP10 AL538781 dipeptidyl-peptidase 10 proteolysisskeletal development 225720_at 5.3 SYNPO2 AW009747 synaptopodin 2 unknown 223395_at 5.3 ABI3BP AB056106 ABI gene family, member 3 (NESH) binding protein unknown 223730_at 5.3 GPC6 AF111178 6 unknown 228716_at 5.2 THRB BG494007 thyroid , beta (erythroblastic leukemia viral (v-erb-a) oncogene regulation of transcription, DNA-dependent / sensory perception of sound homolog 2, avian) 219563_at 5.2 C14orf139 NM_024633 open reading frame 139 unknown 202555_s_at 5.2 MYLK NM_005965 myosin, polypeptide kinase protein amino acid phosphorylation 231120_x_at 5.2 PKIB AL569326 protein kinase (cAMP-dependent, catalytic) inhibitor beta negative regulation of protein kinase activity 225381_at 5.1 LOC399959 AW162210 hypothetical gene supported by BX647608 unknown 204818_at 5.1 HSD17B2 NM_002153 hydroxysteroid (17-beta) dehydrogenase 2 estrogen biosynthesis / metabolism / steroid biosynthesis / lipid biosynthesis 220074_at 5.1 MUCDHL NM_017717 mucin and cadherin-like cell adhesion 213716_s_at 5.1 SECTM1 BF939675 secreted and transmembrane 1 immune response / mesoderm development / positive regulation of I-kappaB kinase/NF-kappaB cascade 1554007_at 5.1 ZNF483 BC036488 Zinc finger protein 483 regulation of transcription, DNA-dependent 1566115_at 5.1 NEDD4L AL833742 Neural precursor cell expressed, developmentally down-regulated 4-like sodium ion transport / sodium ion homeostasis / excretion / response to metal ion / protein ubiquitination / water homeostasis / regulation of protein catabolism / positive regulation of endocytosis / protein modification 219867_at 5.0 CHODL NM_024944 chondrolectin muscle development 229947_at 5.0 PI15 AI088609 peptidase inhibitor 15 unknown 238441_at 5.0 AI928203 CDNA clone IMAGE:5288757 unknown 231580_at 5.0 AI676062 EST unknown 238533_at 5.0 EPHA7 AA651750 EPH receptor A7 protein amino acid phosphorylation / transmembrane receptor protein tyrosine kinase signaling pathway 205924_at 5.0 RAB3B BC005035 RAB3B, member RAS oncogene family small GTPase mediated signal transduction / protein transport 204042_at 5.0 WASF3 AB020707 WAS , member 3 protein complex assembly / actin filament polymerization 228507_at 5.0 AI742043 CDNA FLJ37884 fis, clone BRSTN2012451 unknown 229584_at 5.0 LRRK2 AK026776 leucine-rich repeat kinase 2 protein amino acid phosphorylation / small GTPase mediated signal transduction / protein transport 205614_x_at 5.0 MST1 NM_020998 macrophage stimulating 1 (-like) proteolysis / blood coagulation 227354_at 5.0 PAG1 BF589359 phosphoprotein associated with glycosphingolipid microdomains 1 immune response 205804_s_at 5.0 TRAF3IP3 NM_025228 TRAF3 interacting protein 3 unknown 206054_at 4.9 KNG NM_000893 1 smooth muscle contraction / inflammatory response / negative regulation of cell adhesion / diuresis / natriuresis / negative regulation of blood coagulation / vasodilation / positive regulation of apoptosis / regulation of blood vessel size 1553559_at 4.9 LOC134285 NM_173490 proline-rich protein PRP2 unknown 218870_at 4.9 ARHGAP15 NM_018460 Rho GTPase activating protein 15 regulation of cell shape 218756_s_at 4.9 MGC4172 NM_024308 short-chain dehydrogenase/reductase metabolism 204359_at 4.9 FLRT2 NM_013231 fibronectin leucine rich transmembrane protein 2 cell adhesion 229936_at 4.9 GFRA3 AA694259 GDNF family receptor alpha 3 signal transduction / peripheral nervous system development 219737_s_at 4.9 PCDH9 AI524125 protocadherin 9 cell adhesion 229288_at 4.9 BF439579 EST unknown 239296_at 4.8 ZFHX1B AI623184 Zinc finger homeobox 1b regulation of transcription, DNA-dependent / nervous system development 205945_at 4.8 IL6R NM_000565 interleukin 6 receptor immune response / cell surface receptor linked signal transduction / development / cell proliferation 243780_at 4.8 AW575863 CDNA FLJ46553 fis, clone THYMU3038879 unknown 206710_s_at 4.8 EPB41L3 NM_012307 erythrocyte membrane protein band 4.1-like 3 cortical actin cytoskeleton organization and biogenesis 230117_at 4.8 LOC285878 AI420977 hypothetical protein LOC285878 unknown 219368_at 4.8 NAP1L2 NM_021963 nucleosome assembly protein 1-like 2 nucleosome assembly 206310_at 4.8 SPINK2 NM_021114 serine peptidase inhibitor, Kazal type 2 (acrosin-trypsin inhibitor) unknown 219837_s_at 4.7 CYTL1 NM_018659 cytokine-like 1 signal transduction 1405_i_at 4.7 CCL5 M21121 chemokine (C-C motif) ligand 5 calcium ion homeostasis / exocytosis / cell motility / chemotaxis / inflammatory 205200_at 4.7 CLEC3B NM_003278 C-type lectin domain family 3, member B skeletalresponse development / cellular defense response / response to oxidative stress / cell 201044_x_at 4.7 DUSP1 AA530892 dual specificity phosphatase 1 protein amino acid dephosphorylation / response to oxidative stress / cell cycle 204036_at 4.7 EDG2 AW269335 endothelial differentiation, lysophosphatidic acid G-protein-coupled receptor, 2 signal transduction / G-protein coupled receptor protein signaling pathway / phospholipase C activation / elevation of cytosolic calcium ion concentration / positive regulation of I-kappaB kinase/NF-kappaB cascade 213155_at 4.7 KIAA0523 AB011095 KIAA0523 protein unknown 206001_at 4.7 NPY NM_000905 calcium ion transport / cell motility / G-protein signaling, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / synaptic transmission / digestion / feeding behavior / circulation / cell proliferation 219064_at 4.7 ITIH5 NM_030569 inter-alpha (globulin) inhibitor H5 hyaluronan metabolism 1554522_at 4.7 CNNM2 BC021222 cyclin M2 unknown 206201_s_at 4.7 MEOX2 NM_005924 mesenchyme homeobox 2 regulation of transcription, DNA-dependent / development / circulation 221748_s_at 4.7 TNS1 AL046979 tensin 1 intracellular signaling cascade 213423_x_at 4.7 TUSC3 AI884858 tumor suppressor candidate 3 electron transport / protein amino acid N-linked glycosylation via asparagine 208335_s_at 4.6 DARC NM_002036 Duffy blood group, defense response / signal transduction / G-protein coupled receptor protein signaling pathway 229400_at 4.6 HOXD10 AW299531 homeobox D10 regulation of transcription, DNA-dependent / development 206623_at 4.6 PDE6A NM_000440 phosphodiesterase 6A, cGMP-specific, rod, alpha signal transduction / visual perception / response to stimulus 207254_at 4.6 SLC15A1 NM_005073 solute carrier family 15 (oligopeptide transporter), member 1 peptide transport / digestion / protein transport 207245_at 4.6 UGT2B17 NM_001077 UDP glucuronosyltransferase 2 family, polypeptide B17 metabolism / steroid metabolism 205896_at 4.6 SLC22A4 NM_003059 solute carrier family 22 (organic cation transporter), member 4 nucleosome assembly / sodium ion transport / fluid secretion / organic cation transport Supplementary Table 4, page 6 218999_at 4.6 TMEM140 NM_018295 transmembrane protein 140 unknown 227758_at 4.6 RERG AW294092 RAS-like, estrogen-regulated, growth inhibitor small GTPase mediated signal transduction / negative regulation of cell 219230_at 4.6 TMEM100 NM_018286 transmembrane protein 100 unknownproliferation / response to hormone stimulus / negative regulation of cell growth 227048_at 4.5 LAMA1 AI990816 laminin, alpha 1 development / regulation of cell adhesion / regulation of cell migration / regulation

of embryonic development / positive regulation of epithelial cell proliferation 236300_at 4.5 BF698797 CDNA FLJ37884 fis, clone BRSTN2012451 unknown 205430_at 4.5 BMP5 AL133386 bone morphogenetic protein 5 ossification / cell differentiation / growth / cartilage development / skeletal development 209550_at 4.5 NDN U35139 necdin homolog (mouse) regulation of progression through cell cycle / regulation of cell growth / regulation of transcription, DNA-dependent / nervous system development / negative regulation of cell proliferation 229327_s_at 4.5 BE674528 Strongly similar to NP_005351.2 v- musculoaponeurotic fibrosarcoma oncogene unknown 213217_at 4.5 ADCY2 AU149572 homologadenylate [H.cyclase sapiens] 2 (brain) cAMP biosynthesis / intracellular signaling cascade / cyclic nucleotide biosynthesis 219279_at 4.5 DOCK10 NM_017718 dedicator of cytokinesis 10 unknown 228766_at 4.5 AW299226 EST unknown 201843_s_at 4.5 EFEMP1 NM_004105 EGF-containing fibulin-like extracellular matrix protein 1 visual perception 229916_at 4.5 ENPP6 AU146204 ectonucleotide pyrophosphatase/phosphodiesterase 6 nucleotide metabolism 201141_at 4.5 GPNMB NM_002510 glycoprotein (transmembrane) nmb negative regulation of cell proliferation 241703_at 4.5 RPIB9 AI928037 Rap2-binding protein 9 unknown 241457_at 4.4 FBXL7 AI821935 F-box and leucine-rich repeat protein 7 ubiquitin-dependent protein catabolism 236389_x_at 4.4 OIT3 T90064 Oncoprotein induced transcript 3 unknown 210670_at 4.4 PPY M15788 digestion / protein secretion 202992_at 4.4 C7 NM_000587 complement activation / response to pathogenic bacteria / cytolysis / innate immune response 228194_s_at 4.4 SORCS1 AI675836 sortilin-related VPS10 domain containing receptor 1 intracellular protein transport / neuropeptide signaling pathway 229337_at 4.4 USP2 AW274034 ubiquitin specific peptidase 2 ubiquitin-dependent protein catabolism 224355_s_at 4.4 MS4A8B AF237905 membrane-spanning 4-domains, subfamily A, member 8B signal transduction 232235_at 4.4 C18orf4 AK021539 open reading frame 4 unknown 231093_at 4.4 FCRH3 BF514552 Fc receptor-like 3 unknown 209465_x_at 4.4 PTN AL565812 pleiotrophin (heparin binding growth factor 8, neurite growth-promoting factor 1) regulation of progression through cell cycle / transmembrane receptor protein tyrosine phosphatase signaling pathway / nervous system development / positive regulation of cell proliferation 205551_at 4.4 SV2B NM_014848 synaptic vesicle glycoprotein 2B transport 206641_at 4.4 TNFRSF17 NM_001192 tumor necrosis factor receptor superfamily, member 17 immune response / signal transduction / development / cell proliferation / antimicrobial humoral response 227478_at 4.4 LOC284262 BF739885 hypothetical protein LOC284262 unknown 212956_at 4.4 TBC1D9 AI348094 TBC1 domain family, member 9 unknown 204749_at 4.3 NAP1L3 NM_004538 nucleosome assembly protein 1-like 3 nucleosome assembly 209813_x_at 4.3 TRGV9 M16768 T cell receptor gamma variable 9 cellular defense response / immune response 220068_at 4.3 VPREB3 NM_013378 pre-B lymphocyte gene 3 unknown 205484_at 4.3 SIT NM_014450 signaling threshold regulating transmembrane adaptor 1 immune response / signal transduction / regulation of T cell activation 221019_s_at 4.3 COLEC12 NM_030781 sub-family member 12 /// collectin sub-family member 12 , recognition / carbohydrate mediated signaling / antibacterial humoral response / antifungal humoral response / innate immune response / oxidized low-density lipoprotein catabolism / protein homooligomerization / phagocytosis, recognition / phosphate transport / defense response / carbohydrate mediated signaling / oxidized low-density lipoprotein catabolism 205653_at 4.3 CTSG NM_001911 cathepsin G proteolysis / immune response 204894_s_at 4.3 AOC3 NM_003734 amine oxidase, copper containing 3 (vascular adhesion protein 1) inflammatory response / cell adhesion / amine metabolism 213509_x_at 4.3 CES2 AW157619 carboxylesterase 2 (intestine, ) catabolism 219895_at 4.3 FAM70A NM_017938 family with sequence similarity 70, member A unknown 1552673_at 4.3 RFXDC1 NM_173560 regulatory domain containing 1 regulation of transcription, DNA-dependent / tRNA splicing 220303_at 4.3 PDZD3 NM_024791 PDZ domain containing 3 receptor guanylyl cyclase signaling pathway 236783_at 4.3 KCNIP4 AI732844 Kv channel interacting protein 4 potassium ion transport 230087_at 4.3 PRIMA1 AI823645 proline rich membrane anchor 1 neurotransmitter catabolism 203485_at 4.3 RTN1 NM_021136 reticulon 1 signal transduction / neuron differentiation 227530_at 4.2 AKAP12 BF511276 A kinase (PRKA) anchor protein (gravin) 12 protein targeting / signal transduction / G-protein coupled receptor protein signaling pathway 205627_at 4.2 CDA NM_001785 cell surface receptor linked signal transduction / pyrimidine salvage // cytidine deamination / cytosine metabolism / negative regulation of cell growth / negative regulation of granulocyte differentiation / negative regulation of nucleotide metabolism / cytidine metabolism / protein homotetramerization 204584_at 4.2 L1CAM AI653981 L1 cell adhesion molecule cell adhesion / nervous system development / cell differentiation 1554012_at 4.2 RSPO2 BC027938 R-spondin 2 homolog (Xenopus laevis) unknown 220146_at 4.2 TLR7 NM_016562 toll-like receptor 7 inflammatory response / immune response 243806_at 4.2 AW015140 EST unknown 243366_s_at 4.2 CERKL AI936034 Ceramide kinase-like protein kinase C activation / visual perception / response to stimulus 212827_at 4.2 IGHM X17115 immunoglobulin heavy constant mu immune response / antigen presentation, endogenous antigen / antigen processing, endogenous antigen via MHC class I 244741_s_at 4.2 MGC9913 BE855713 hypothetical protein MGC9913 unknown 229127_at 4.2 ATP5J BF195118 ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F6 generation of precursor metabolites and energy / ion transport / ATP synthesis coupled proton transport / proton transport 212192_at 4.2 KCTD12 AI718937 potassium channel tetramerisation domain containing 12 potassium ion transport 209842_at 4.2 SOX10 AI367319 SRY (sex determining region Y)-box 10 regulation of transcription from RNA polymerase II promoter / sensory perception of sound / morphogenesis / regulation of transcription, DNA-dependent 223618_at 4.2 FMN2 AF225426 formin 2 intracellular signaling cascade / development / cell organization and biogenesis / actin cytoskeleton organization and biogenesis 238512_at 4.1 ST7L BF961733 Suppression of tumorigenicity 7 like unknown 233269_at 4.1 AK000085 CDNA FLJ20078 fis, clone COL02974 unknown 222043_at 4.1 CLU AI982754 lipid metabolism / apoptosis / complement activation,/ fertilization / cell death / innate immune response 220421_at 4.1 BTNL8 NM_024850 butyrophilin-like 8, similar to butyrophilin 3 unknown 229084_at 4.1 CNTN4 R42166 contactin 4 cell adhesion / neuron adhesion / nervous system development / axon guidance / axonal fasciculation / brain development / negative regulation of neuron differentiation / regulation of synaptic plasticity / neurite development / axonogenesis 1554547_at 4.1 FAM13C1 BC036453 family with sequence similarity 13, member C1 unknown 211719_x_at 4.1 FN1 BC005858 fibronectin 1 /// fibronectin 1 acute-phase response / cell adhesion / transmembrane receptor protein tyrosine

kinase signaling pathway / metabolism / response to wounding / cell migration 201348_at 4.1 GPX3 NM_002084 glutathione peroxidase 3 (plasma) response to lipid hydroperoxide / hydrogen peroxide catabolism / protein homotetramerization / response to oxidative stress 207957_s_at 4.1 PRKCB1 NM_002738 Protein kinase C, beta 1 protein amino acid phosphorylation / intracellular signaling cascade / signal transduction 235146_at 4.1 N51717 EST unknown 209555_s_at 4.1 CD36 M98399 CD36 molecule (thrombospondin receptor) lipid metabolism / fatty acid metabolism / transport / cell adhesion / blood coagulation 228399_at 4.1 OSR1 AI569974 odd-skipped related 1 (Drosophila) unknown 236293_at 4.1 RHOH BE676335 Ras homolog gene family, member H small GTPase mediated signal transduction / T cell differentiation / negative regulation of I-kappaB kinase/NF-kappaB cascade / regulation of transcription 217143_s_at 4.1 TRA@, TRD@ X06557 T cell receptor alpha locus /// T cell receptor delta locus cellular defense response / immune response 204118_at 4.1 CD48 NM_001778 CD48 molecule /// CD48 molecule defense response 206633_at 4.1 CHRNA1 NM_000079 cholinergic receptor, nicotinic, alpha 1 (muscle) ion transport / muscle contraction / signal transduction Supplementary Table 4, page 7 226186_at 4.1 TMOD2 AW207699 2 (neuronal) nervous system development 242715_at 4.1 AA331548 Strongly similar to XP_541723.2 PREDICTED: similar to zinc finger protein 536 unknown 203766_s_at 4.1 LMOD1 NM_012134 [Canisleiomodin familiaris] 1 (smooth muscle) unknown 230595_at 4.1 LOC572558 BF677651 hypothetical locus LOC572558 unknown 204961_s_at 4.1 NCF1 NM_000265 neutrophil cytosolic factor 1 (47kDa, chronic granulomatous disease, autosomal 1) electron transport / superoxide metabolism / cellular defense response /

intracellular signaling cascade / oxygen and reactive oxygen species metabolism 219670_at 4.0 C1orf165 NM_024603 open reading frame 165 proteolysis 209540_at 4.0 IGF1 AU144912 insulin-like growth factor 1 (somatomedin C) skeletal development / DNA replication / cell motility / Ras protein signal transduction / muscle development / physiological process / sensory perception of sound / positive regulation of cell proliferation / glycolate metabolism 1555465_at 4.0 MCOLN2 AY083533 mucolipin 2 cation transport 206407_s_at 4.0 CCL13 NM_005408 chemokine (C-C motif) ligand 13 calcium ion homeostasis / chemotaxis / inflammatory response / signal transduction / cell-cell signaling / response to stimulus / immune response

* compared with expression in normal mucosa Supplementary Table 5: Genes known to be targets of Wnt/β-catenin signaling # Gene Symbol Gene Name Ref. ABCB1 (MDR1) ATP-binding cassette, sub-family B (MDR/TAP), member 1 * APCDD1 adenomatosis polyposis coli down-regulated 1 1 ASCL2 achaete-scute complex-like 2 (Drosophila) 2 ATOH1 (Hath1) Homo sapiens atonal homolog 1 (Drosophila) (ATOH1), mRNA. * AXIN2 axin 2 (conductin, axil) * BGLAP bone gamma-carboxyglutamate (gla) protein (osteocalcin) * BIRC5 baculoviral IAP repeat-containing 5 (survivin) * BMP4 bone morphogenetic protein 4 * BTRC beta-transducin repeat containing * CCND1 cyclin D1 (PRAD1: parathyroid adenomatosis 1) * CD24 CD24 antigen (small cell lung carcinoma cluster 4 antigen) 3 CD44 CD44 antigen (homing function and Indian blood group system) * CDH1 cadherin 1, type 1, E-cadherin (epithelial) * CDX4 caudal type homeo box transcription factor 4 * CLDN1 claudin 1 * CSPG2 chondroitin sulfate proteoglycan 2 (versican) * CST1 cystatin SN 4 CTGF connective tissue growth factor * CYR61 cysteine-rich, angiogenic inducer, 61 * DKK1 dickkopf homolog 1 (Xenopus laevis) * DLL1 delta-like 1 (Drosophila) * DRCTNNB1A down-regulated by Ctnnb1, a 5 EDA ectodysplasin A * EDAR ectodysplasin 1, anhidrotic receptor * EDN1 endothelin 1 * EDN3 endothelin 3 4 EFNB1 ephrin-B1 * EGFR epidermal growth factor receptor * EMP1 epithelial membrane protein 1 * EN2 engrailed homolog 2 * ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin) * EPHB2 EPH receptor B2 * EPHB3 EPH receptor B3 * ETV4 ets variant gene 4 (E1A enhancer binding protein, E1AF) 6 FGF18 fibroblast growth factor 18 * FGF20 fibroblast growth factor 20 * FGF4 fibroblast growth factor 4 * FGF9 fibroblast growth factor 9 (glia-activating factor) * FN1 fibronectin 1 * FOSL1 (fra-1) FOS-like antigen 1 * FOXN1 forkhead box N1 * FST follistatin * FZD7 frizzled homolog 7 (Drosophila) * GAS gastrin * GCG glucagon * GJA1 gap junction protein, alpha 1, 43kDa (connexin 43) * GJB6 gap junction protein, beta 6 (connexin 30) * HIG2 hypoxia-inducible protein 2 7 Supplementary Table 5, page 2 HSPG2 heparan sulfate proteoglycan 2 (perlecan) * ID2 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein * IGF1 insulin-like growth factor 1 (somatomedin C) * IGF2 insulin-like growth factor 2 (somatomedin A) * IGFBP2 insulin-like growth factor binding protein 2, 36kDa 8 IL6 interleukin 6 (interferon, beta 2) * IL8 interleukin 8 * IRX3 iroquois homeobox protein 3 * ISLR immunoglobulin superfamily containing leucine-rich repeat * JUN v-jun sarcoma virus 17 oncogene homolog (avian) * KLF5 (BTEB2) Kruppel-like factor 5 (intestinal) * KRTHB6 keratin, hair, basic, 6 (monilethrix) * L1CAM L1 cell adhesion molecule * LEF1 lymphoid enhancer-binding factor 1 * LGR5 leucine-rich repeat-containing G protein-coupled receptor 5 9 LRP5 low density lipoprotein receptor-related protein 5 * LRP6 low density lipoprotein receptor-related protein 6 * MET met proto-oncogene (hepatocyte growth factor receptor) * MITF microphthalmia-associated transcription factor * MMP26 matrix metalloproteinase 26 * MMP3 matrix metalloproteinase 3 (stromelysin 1, progelatinase) * MMP7 matrix metalloproteinase 7 (matrilysin, uterine) * MSLN mesothelin * MSX1 msh homeo box homolog 1 (Drosophila) 10 MSX2 msh homeo box homolog 2 (Drosophila) 10 MYC v-myc myelocytomatosis viral oncogene homolog (avian) * MYCBP c-myc binding protein * NEUROG1 neurogenin 1 * NKD1 naked cuticle homolog 1 (Drosophila) * NKD2 naked cuticle homolog 2 (Drosophila) * NLK nemo like kinase * NRCAM neuronal cell adhesion molecule * OVOL1 (movo1) ovo-like 1(Drosophila) * PITX2 paired-like homeodomain transcription factor 2 * PLAUR (uPar) plasminogen activator, urokinase receptor * POSTN periostin, osteoblast specific factor * PPARD (PPARd) peroxisome proliferative activated receptor, delta * PTGS2 (COX-2) prostaglandin-endoperoxide synthase 2 * PTTG1 pituitary tumor-transforming 1 * RARG retinoic acid receptor, gamma * RET ret proto-oncogene * RHOU (Wrch-1) ras homolog gene family, member U * RUNX2 runt-related transcription factor 2 * SFRP2 secreted frizzled-related protein 2 * SIX3 sine oculis homeobox homolog 3 (Drosophila) * SOX2 SRY (sex determining region Y)-box 2 * SOX4 SRY (sex determining region Y)-box 4 11 SOX9 SRY (sex determining region Y)-box 9 * SP5 Sp5 transcription factor 12 Supplementary Table 5, page 3 STRA6 stimulated by retinoic acid gene 6 * T (Brachyury) T, brachyury homolog (mouse) * TCF1 transcription factor 1, hepatic; LF-B1, hepatic nuclear factor (HNF1) * TCF4 (ITF2) transcription factor 4 * TIAM1 T-cell lymphoma invasion and metastasis 1 * TNFSF11 (RANKL) tumor necrosis factor (ligand) superfamily, member 11 * TNFSF9 (4-1BBL) tumor necrosis factor (ligand) superfamily, member 9 * TWIST1 twist homolog 1 (acrocephalosyndactyly 3; Saethre-Chotzen syndrome) * UBXD1 UBX domain containing 1 * VEGF vascular endothelial growth factor * VEGFC vascular endothelial growth factor C * WISP1 WNT1 inducible signaling pathway protein 1 * WISP2 WNT1 inducible signaling pathway protein 2 *

# This gene list is based on the data of R. Nusse (http://www.stanford.edu/~rnusse/pathways/targets.html and http://www.stanford.edu/~rnusse/pathways/targetcomp.html (studies referenced with *) and those reported in the references listed below. The is not intended to be comprehensive and does not include genes identified as putative Wnt targets in gene expression studies.

01. Cancer Res. 2002;62:5651-5656. 02. Oncogene. 2006;25:3445-3457. 03. Oncogene. 2006;25:4361-4369. 04. Cancer Res. 2003;63:2913-2922. 05. Cancer Res. 2000;60:3354-3358 06. Am J Pathol. 2002;160:2181-2190. 07. BMC Cancer. 2005;5:3. 08. Oncogene. 2005;24:3141-3153. 09. Hepatology. 2003;37:528-533. 10. BMC Dev Biol. 2002;2:8. 11. Cancer Res. 2005;65:166-176. 12. Int J Oncol. 2005;27:1483-1487. Supplementary Table 6. Genes classified as transcription regulators (by Gene Ontology) with significantly altered expression in colorectal adenomas, compared with normal mucosa (fold changes 2-4). (Genes with fold changes > 4 are reported in Table 2). Gene Symbol Gene Name Fold Differences * ▲ ▼ TRIP13 interactor 13 3.5 SOX1 SRY (sex determining region Y)-box 1 3.4 MYCN v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian) 3.4 TRIP6 thyroid hormone receptor interactor 6 3.4 GTF2IRD1 GTF2I repeat domain containing 1 3.3 PML promyelocytic leukemia 3.2 KIAA1549 KIAA1549 protein 3.2 MYC v-myc myelocytomatosis viral oncogene homolog (avian) 3.2 ID4 inhibitor of DNA binding 4, dominant negative helix-loop-helix protein 3.1 HOXB8 homeobox B8 3.0 MYBL2 v- myeloblastosis viral oncogene homolog (avian)-like 2 3.0 ATOH8 atonal homolog 8 (Drosophila) 2.9 TRIM16 tripartite motif-containing 16 2.9 PITX1 paired-like homeodomain transcription factor 1 2.9 ZNF367 zinc finger protein 367 2.9 TFAP2A transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha) 2.8 SOX4 SRY (sex determining region Y)-box 4 2.8 FOXM1 forkhead box M1 2.7 SOX9 SRY (sex determining region Y)-box 9 2.7 DDB2 damage-specific DNA binding protein 2, 48kDa 2.7 HOXB6 homeobox B6 2.7 NME1 non-metastatic cells 1, protein (NM23A) expressed in 2.7 PIR pirin (iron-binding nuclear protein) 2.6 FOSL1 FOS-like antigen 1 2.6 UHRF1 ubiquitin-like, containing PHD and RING finger domains, 1 2.6 TGIF TGFB-induced factor (TALE family homeobox) 2.4 ETS2 v-ets erythroblastosis virus E26 oncogene homolog 2 (avian) 2.4 HES4 hairy and enhancer of split 4 (Drosophila) 2.4 E2F7 transcription factor 7 2.4 NPM1 nucleophosmin (nucleolar phosphoprotein B23, numatrin) 2.4 PTTG1 pituitary tumor-transforming 1 2.3 ZNF593 zinc finger protein 593 2.3 TCF3 transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47) 2.3 BRCA2 breast cancer 2, early onset 2.3 ID1 inhibitor of DNA binding 1, dominant negative helix-loop-helix protein 2.3 BRCA1 breast cancer 1, early onset 2.3 BHLHB2 basic helix-loop-helix domain containing, class B, 2 2.2 ERCC2 excision repair cross-complementing rodent repair deficiency, complem. group 2 2.2 MYBBP1A MYB binding protein (P160) 1a 2.2 HOXA9 homeobox A9 2.2 HMGA1 high mobility group AT-hook 1 2.1 GTF3A general transcription factor IIIA 2.1 PROX1 Prospero-related homeobox 1 2.1 YEATS4 YEATS domain containing 4 2.1 CRSP8 required for Sp1 transcriptional activation, subunit 8, 34kDa 2.0 DMRTA2 DMRT-like family A2 2.0 TCF12 transcription factor 12 (HTF4, helix-loop-helix transcription factors 4) 2.0 EBF early B-cell factor 3.9 ZFPM2 zinc finger protein, multitype 2 3.8 GAS7 growth arrest-specific 7 3.8 SNAI2 snail homolog 2 (Drosophila) 3.8 RUNX1T1 runt-related transcription factor 1; translocated to, 1 (cyclin D-related) 3.6 MAF v-maf musculoaponeurotic fibrosarcoma oncogene homolog (avian) 3.6 TCF21 transcription factor 21 3.6 NR3C2 Nuclear receptor subfamily 3, group C, member 2 3.5 BACH2 BTB and CNC homology 1, basic leucine zipper transcription factor 2 3.4 MXD1 MAX dimerization protein 1 3.3 DES / FAM48A / family with sequence similarity 48, member A 3.2 MEF2C MADS box transcription enhancer factor 2, C (myocyte enhancer factor 2C) 3.1 PEG3 paternally expressed 3 3.1 TFCP2L1 Transcription factor CP2-like 1 3.1 FOXO1A Forkhead box O1A (rhabdomyosarcoma) 3.1 HOXD1 homeobox D1 3.1 TNFRSF7 tumor necrosis factor receptor superfamily, member 7 3.0 TBX10 T-box 10 3.0 FOXP2 Forkhead box P2 3.0 HLF hepatic leukemia factor 3.0 ARX aristaless related homeobox 3.0 HDAC9 histone deacetylase 9 3.0 ABP1 Amiloride binding protein 1 (amine oxidase (copper-containing)) 2.9 ALF TFIIA-alpha/beta-like factor 2.9 MXI1 MAX interactor 1 2.9 HOXD11 homeobox D11 2.9 HOXA1 2.9 IRF4 interferon regulatory factor 4 2.8 Supplementary Table 6, page2 FLI1 Friend leukemia virus integration 1 2.8 RORB RAR-related orphan receptor B 2.8 HOXB13 homeobox B13 2.8 HIVEP3 Human immunodeficiency virus type I enhancer binding protein 3 2.8 RAXLX RAX-like homeobox 2.7 MAFB v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (avian) 2.7 NR2C2 Nuclear receptor subfamily 2, group C, member 2 2.6 PPARGC1B peroxisome proliferative activated receptor, gamma, coactivator 1, beta 2.6 ZBTB16 zinc finger and BTB domain containing 16 2.6 HCLS1 hematopoietic cell-specific Lyn substrate 1 2.6 PBX1 Pre-B-cell leukemia transcription factor 1 2.6 HOXD4 homeobox D4 2.6 SP140 SP140 nuclear body protein 2.6 Kruppel-like factor 4 (gut) 2.5 ZNF91 zinc finger protein 91 2.5 CITED2 Cbp/p300-interacting transactivator, Glu/Asp-rich carboxy-terminal domain, 2 2.5 HNF4A hepatocyte nuclear factor 4, alpha 2.5 TCF4 transcription factor 4 2.5 TRPS1 trichorhinophalangeal syndrome I 2.5 TRERF1 Transcriptional regulating factor 1 2.4 TSC22D3 TSC22 domain family, member 3 2.4 GLI2 GLI-Kruppel family member GLI2 2.4 FOXF2 forkhead box F2 2.4 NKX2-2 NK2 transcription factor related, locus 2 (Drosophila) 2.4 ETV1 ets variant gene 1 2.3 WWTR1 WW domain containing transcription regulator 1 2.3 ELL2 Elongation factor, RNA polymerase II, 2 2.3 ETS1 V-ets erythroblastosis virus E26 oncogene homolog 1 (avian) 2.3 POU2AF1 POU domain, class 2, associating factor 1 2.3 LRRFIP1 Leucine rich repeat (in FLII) interacting protein 1 2.3 HOP homeodomain-only protein 2.2 MITF microphthalmia-associated transcription factor 2.2 HHEX homeobox, hematopoietically expressed 2.2 HOXA5 homeobox A5 2.2 PIAS1 Protein inhibitor of activated STAT, 1 2.2 LMO3 LIM domain only 3 (rhombotin-like 2) 2.2 HOXA2 homeobox A2 2.2 GLI1 glioma-associated oncogene homolog 1 (zinc finger protein) 2.1 KLF10 Kruppel-like factor 10 2.1 GATA3 GATA binding protein 3 2.1 KLF9 Kruppel-like factor 9 2.1 TCF2 transcription factor 2, hepatic; LF-B3; variant hepatic nuclear factor 2.1 SALL2 sal-like 2 (Drosophila) 2.1 PCAF p300/CBP-associated factor 2.1 ZNFN1A1 zinc finger protein, subfamily 1A, 1 (Ikaros) 2.1 RORA RAR-related orphan receptor A 2.1 DSCR1 Down syndrome critical region gene 1 2.1 NOTCH2 Notch homolog 2 (Drosophila) 2.1 FOXF1 forkhead box F1 2.1 EPAS1 Endothelial PAS domain protein 1 2.1 SATB2 SATB family member 2 2.0 RUNX1 Runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) 2.0 VDR vitamin D (1,25- dihydroxyvitamin D3) receptor 2.0

* Overexpressed (▲) or underexpressed (▼) in adenomas (vs. normal mucosa samples)