Transcription Profile of HTLV-I-Infected Cells Compared to Activated Lymphocytes

Cynthia A. Pise-Masison1, Michael Radonovich1, Renaud Mahieux2, Pramita Chatterjee1, Craig Whiteford3, Janet Duvall1, Claire Guillerm1, Antoine Gessain2, and John N. Brady1*

1Basic Research Laboratory, Virus Tumor Biology Section, National Cancer Institute, 9000 Rockville Pike, Bethesda, MD 20892, 2Unite d'Epidemiologie et Physiopathologie des Virus Oncogenes, Batiment SIDA-Retrovirus, 28, rue du Dr Roux, Institut Pasteur, 75724 Paris cedex 15, 3ATC, National Institutes of Health, Gaithersburg, MD, 20805

*Corresponding Author: [email protected]; tel.:(301)496-0986; fax.:(301)496-4951 [email protected]; tel: (301)435-2499; fax: (301)496-4951 [email protected]; tel: (301)496-4953;fax: (301)496-4951 [email protected]; tel: (33)-1-45-68-89-06;fax: (33)-1- 40-61-34-65 [email protected]; tel: (301)496-4793;fax: (301)496-4951 [email protected]; tel: (301)402-9217;fax: (301)496-4951 [email protected]; tel: (301)435-2501; fax: (301)496-4951 [email protected]; tel: (301)496-0988;fax: (301)496-4951 [email protected]; tel: (33)-1-45-68-89-06;fax: (33)-1- 40-61-34-65

Running title: Expression Profiles of HTLV-I-Infected Cells

Key Words: HTLV-I, ATL, Transcription, Microarray,

1 Supplementary Table. A list of the 763 differentially expressed in the HTLV-I-infected cells compared to activated donor peripheral blood lymphocytes (PBLs), listed by category. All genes listed were expressed either 2-fold or greater (increased) or 2-fold or less (decreased) in comparison to activated PBLs. Indicated by gray shading, genes already identified as differentially expressed in microarray studies are listed.

GenBank Acc. No. Gene Description Citationa

Harhaj de La Ruckes et.al. Fuente et.al. et. al. Increased Genes Transcription factors AD000092_cds7_s_at AF005887_at (ATF6) CREB binding serum response factor D14826_s_at (CREM) cAMP responsive element modulator D87673_at (HSF4) heat shock transcription factor 4 D90070_s_at (APR) PMA induced mRNA D90224_at (TNFSF4) tumor necrosis factor (ligand) superfamily up up gp34 J04076_at early growth response 2 (Krox-20 homolog) up J04102_at ETS2 up J04111_at c-Jun up L19871_at (ATF3) activating transcription factor 3 L23587_at DP-1 up L34587_at putative gene up L37936_at elongation factor Ts L40386_s_at DP-2 L46353_at HMG1-C M16038_at Lyn M37583_at (H2AFZ) M57732_at transcription factor 1, hepatic; LF-B1, HNF1 M61156_at (TFAP2A) transcription factor AP-2 alpha M62810_at transcription factor 6-like 1 up M69043_at (NFKBIA) IKB alpha M74719_at (TCF4) transcription factor 4 M77810_at GATA-2 up M92357_at B94 up S73205_at (INSAF) insulin activator factor U15460_at B-ATF U20734_s_at JunB up U24166_at EB1 U51127_at (IRF5) interferon regulatory factor 5 U52682_at (IRF4) interferon regulatory factor 4 U59863_at (I-TRAF) U91616_at (NFKBIE) cytoplasmic NFkB inhibitor epsilon Receptors/Signaling molecules

2 D26070_at (ITPR1) inositol 1,4,5-triphosphate , type 1 D38076_at (RANBP1) D38128_at (PTGIR) prostaglandin I2 (prostacyclin) receptor (IP) D49489_at The transcript is amplified in hydroxyurea-resistant cells D50678_at (LRP8) low density lipoprotein receptor-related 8 J03258_at (VDR) vitamin D (1,25- dihydroxyvitamin D3) receptor K02405_f_at prepeptide MHC HLA-DC3-beta L08069_at (HSJ2) heat shock protein DNAJ-like 2 L08096_at (TNFSF7) CD27 ligand up L08187_at (EBI3) up L08488_at (INPP1) inositol polyphosphate-1- L12723_at (HSPA4) heat shock 70kD protein 4 L13740_at TR3 orphan receptor L19872_at (AHR) aryl hydrocarbon receptor L38608_at (ALCAM) CD6 ligand L40357_at (TRIP7) thyroid hormone receptor interactor 7 L40379_at (TRIP10) thyroid receptor interacting protein 10 L77886_at (PTPRK) protein tyrosine phosphatase, receptor type, K M11058_at (HMGCR)3-hydroxy-3-methylglutaryl-Coenzyme A reductase M11749_at Thy-1 M16276_at (HLA-DQB1) MHC, class II, DQ beta 1 M16441_cds1_ (TNF) tumor necrosis factor (TNF superfamily, member 2) at M22382_at (HSPD1) heat shock protein 60kDa up M23197_at (CD33) M24283_at (ICAM1) intercellular adhesion molecule 1 (CD54) up M26958_at (PTHrP) M33600_f_at (HLA-DRB5) M34996_at cell surface glycoprotein class II M35128_at (CHRM1) cholinergic receptor, muscarinic 1 M57466_s_at (HLA-DPB1) MHC, class II, DP beta 1 M59465_at (A20) TNFAIP1 M62424_at (F2R) coagulation factor II receptor up M83554_at (TNFRSF8) TNF receptor superfamily, member 8 up CD30 M83664_at (HLA-DPB1) MHC, class II, DP beta 1 M83738_at (PTPN9) protein tyrosine phosphatase, non-receptor type 9 M84349_at (CD59) U03398_at (TNFSF9) ILA ligand (TNF related) U07550_at (HSPE1) heat shock protein 10kDa U10550_at (gem) GTPase U12767_at (MINOR) U29343_at (HMMR) hyaluronan-mediated motility receptor (RHAMM) U31628_at (IL15RA) interleukin 15 receptor, alpha U33017_at (SLAM) signaling lymphocytic activation molecule U37546_s_at (API1) apoptosis inhibitor 1 U45983_at (CCR8) U64198_at (IL12RB2) interleukin 12 receptor, beta 2 U68030_at (CCR6) up U70426_at (RGS16) regulator of G-protein signalling 16 U72761_at (KPNB3) beta 3 karyopherin (importin)

3 X00274_at (HLA-DRA) up X01057_at (IL2RA) interleukin 2 receptor, alpha up up X01060_at (TFRC) (p90, CD71) up X02317_at (SOD1) superoxide dismutase up up X02419_rna1_a (PLAU) plasminogen activator, urokinase t X02530_at (INP1-) IFN-induced protein down X02910_at TNF alpha down X03068_f_at precursor class II antigen X03100_cds2_ (HLA-SB) MHC, class II antigen beta at X62744_at (HLA-DM) MHC, class II, DM alpha X77584_at (TXN) thioredoxin Y00636_at (CD58) Z97074_at Rab9 effector GTPase p40 up / AB003698_at (CDC7L1) D10495_at (1-May) Protein C delta up up D10522_at (MACS) MARCKS, 80K-L up J02902_at 2A regulatory alpha subunit L08488_at (INPP1) inositol polyphosphate-1-phosphatase L08835_rna2_a (DMPK) dystrophia myotonica-protein kinase t L11329_at (DUSP2) dual specificity phosphatase 2 up L20320_at (CDK7) cyclin-dependent kinase 7 L37043_at (CSNK1E) , epsilon L76927_rna1_a (GALK1) galactokinase 1 t L77886_at (PTPRK) protein tyrosine phosphatase, receptor type, K M68520_at (CDK2) cyclin-dependent kinase 2 M80359_at (MARK3) MAP/ affinity-regulating kinase 3 U15932_at (DUSP5) dual specificity phosphatase 5 up U37022_rna1_a (CDK4) cyclin-dependent kinase 4 t U43522_at (PTK2B) protein tyrosine kinase 2 beta U48296_at (PTP4A1) protein tyrosine phosphatase type IVA, member 1 U48807_at (DUSP4) dual specificity phosphatase 4 U59919_at (SMAP) Smg GDS-associated protein X02419_rna1_a (PLAU) plasminogen activator, urokinase t X17620_at (NME1) non-metastatic cells 1, protein (NM23A) X54941_at (CKS1) CDC28 protein kinase 1 X54942_at (CKS2) CDC28 protein kinase 2 X56468_at 14.3.3 protein tau X56494_at (PKM2) pyruvate kinase, muscle X89416_at (PPP5) Y00815_at (PTPRF) protein tyrosine phosphatase, receptor type, F Y07604_at (NME4) non-metastatic cells 4 Y10275_at (PSP) phosphoserine phosphatase Z18951_at (CAV1) caveolin 1, caveolae protein, 22kD Cytokines/interleukins/oncogenes

4 D43767_at (SCYA17) small inducible cytokine subfamily A (Cys- up Cys) J00219_at (IFNG) interferon gamma up J04156_at (IL7) interleukin 7 L00058_at c-myc protein, second translated L08187_at (EBI3) cytokine receptor up M13207_at (CSF2) GM-CSF M13755_at (ISG15) IFN-induced 15kDa protein up M14745_at bcl-2 protein up M26062_at (IL2RB) interleukin 2 receptor, beta M28130_at (IL8) interleukin 8 M28209_at (RAB1) RAB1, member RAS oncogene family M28215_at (RAB5A) GTP-binding protein up M30135_at (P40) T-cell and mast cell growth factor precursor M37435_at (CSF1) M57506_rna1_ (SCYA1) I-309 up up up at M57731_at (GRO3) GRO3 oncogene M59941_at (CSF2RB) GM-CSF receptor beta chain M65291_at (IL12A) interleukin 12 A U01038_at (pLK) polo-like kinase up U03397_at (TNFRSF9) ILA U11877_at (IL8RB) interleukin 8 receptor beta U14407_at (IL15) interleukin 15 U31120_rna1_a (IL13) interleukin 13 up t U31628_at (IL15RA) interleukin 15 receptor, alpha U64198_at (IL12RB2) interleukin 12 receptor, beta 2 U83171_at (SCYA22) small inducible cytokine subfamily A (Cys-Cys) X01057_at (IL2RA) interleukin 2 receptor, alpha up up X04602_s_at (IL6) interleukin 6 (interferon, beta 2) up X12794_at (ERBAL2) v-erb-a X51345_at (JUNB) jun B proto-oncogene up 681_s_at (JUND) jun D proto-oncogene X58298 (IL6R) interleukin 6 receptor X67951_at (PAGA) proliferation-associated gene A X75042_at (REL) v-rel avian reticuloendotheliosis viral oncogene up up homolog Y00081_s_at BSF-2/IL6 gene Y10659_at (IL13RA1) interleukin 13 receptor alpha 1 Cell cycle/apoptosis/repair AF005775_at (CFLAR) CASP8 and FADD-like apoptosis regulator D00017_at (ANX2) annexin II D13639 cyclin D2 up up D14878_at (D123) D123 gene product S-phase entry regulator up D21063_at (MCM2) minichromosome maintenance deficient 2 (mitotin) D55716 (P1cdc47) MCM7 D84557_at (HsMcm6) J04611_at (G22P1) 70kDa KU autoantigen J05614_at PCNA L07493_at (RPA3) replication factor

5 L07541_at (RFC3) replication factor 3 up L20320_at (CDK7) cyclin-dependent kinase 7 L25876_at (CIP2) associated with cyclin-dependent kinase M15796_at PCNA M16441_cds1_ (TNF) tumor necrosis factor (TNF superfamily, down at member 2) M17754_at (BN51T) BN51 (BHK21) M25753_at cyclin B1 up up M34065_at (CDC25C) cell division cycle 25C M36089_at (MSH2) X-ray repair complementing defective repair protein up M60974 GADD45 up up M68520_at (CDK2) cyclin-dependent 2 M74093_at (CCNE1) cyclin E1 M87339_at (RFC4) replication factor 4 up M96944_at (BSAP) B-cell specific transcription factor up M97815_at putative CRABP-II retinoic acid binding protein II U03911_at (MSH2) mutS (E. coli) homolog 2 U05340_at (CDC20) up U09579_at p21/CIP1/WAF1 up up up U30872_at mitosin U33286_at (CSE1L) segregation U33761_at (Skp2) cyclin A/CDK2-associated p45 U37022_at (CDK4) cyclin-dependent kinase 4 U37546_s_at (API1) apoptosis inhibitor 1 U37547_at (API2) apoptosis inhibitor 2 U39817_at (BLM) Bloom syndrome U45878_s_at HIAP-1 up up U47414_at cyclin G2 U54778_at 14-3-3 epsilon U77949_at (CDC18L) X05360_at (CDC2) cell division cyle 2 X17644_s_at (GSPT1) G1 to S phase transition 1 X51688 cyclin A up X54941_at (CKS1) CDC28 protein kinase 1 X54942_at (CKS2) CDC28 protein kinase 2 X62048_at Z18951_at (CAV1) caveolin 1, caveolae protein, 22kDa Z23115_at (BCL2L1) Bcl-XL up Miscellaneous AF000430_at -like protein AF001294_at (TSSC3) D00596_at (TYMS) thimidylate synthetase D00760_at (PSMA2) proteasome subunit, A2 D00761_at (PSMB1) proteasome subunit, B1 D00762_at (PSMA3) proteasome subunit, A3 D00763_at (PSMA4) proteasome subunit, A4 D10511_at (PSMC2) proteasome subunit, C2 D13315_at glyoxalose D13627_at (KIAA0002) D13633_at (KIAA0008) D13643_at (KIAA0018)

6 D14660_at (KIAA0104) D14662_at (KIAA0106) D16294-at mitochondrial 3-oxyacyl-CoA thiolase D17400_at (PTS) 6-pyruvoyltetrahydropterin synthase D21267_at (SNAP25) D25274_at RAC1 ras-related C3 botulinum toxin substrate D25547_at PIMT isozyme 1 D26599_at (PSMB2) proteasome subunit B2 D38583_at Calgizzarin D42073_at (RCN1) D43950_at (KIAA0098) D44466_at (PSMD1)proteasome subunit D1 D49396_at (Aop1) D78129_at (SQLE) D78335_at (5' terminal region of UMK) D82346_at (KCNQ2) D83784_at (PLAG2) D87292_at rhodanese D87957_at (RCD1+) HG1111- HT1111_at HG1112- HT1112_at HG1686-HT4572_s_at HG1872- HT1907_at HG1980- HT2023_at HG2383-HT4824_s_at HG274- HT274_s_at HG2855- HT2995_at HG3576-HT3779_f_at HG3921-HT4191_f_at HG4074- HT4344_at HG4157- HT4427_at HG4322- HT4592_at HG688- HT688_f_at J04173_at (PGAM1) phosphoglycerate mutase 1 J04444_at (CYC1) cytochrome c-1 J04456_at (LGALS1) K03021_at (PLAT) plasminogen activator L06132_at (VDAC1) L06419_at (PLOD) L07515_at heterochromatin L07956_at (GBE1)

7 L08666_at (VDAC2) L09229_s_at (FACL1) L11669_at (ADD1) adducin 1 alpha L16842_at (UQCRC1) ubiquinol-cytochrome c reductase core protein L19183_at (MAC30) L29008_at (SORD) L32977_at (UQCRFS1) L36720_at (BYSL) L37368_at RNA binding protein L40377_at (PI9) protease inhibitor 9 L40586_at (IDS) L41668_rna_at (GALE) galactose epimerase L48513_at (PON2) L77701_at x (PON2) M11717_rna1_ (HSPA1L) at M13452_s_at A M13955_at , K7 M14200_rna1_ (DBI) at M18533_at (DMD) M21904_at (MDU1) M22877_at cytochrome c M22976_at (CYB5) cytochrome b5 M23114_at (ATP2A2) M27533_s_at M31642_at (HPRT1) M35878_at (IGFBP3) M36205_at (VAMP2) M36341_at (ARF4) ADP-ribosylation factor 4 M55210_at (LAMC1) B2 chain M55671_at (PROZ) protein z M57710_at (LGALS3) galectin 3 M60858_rna1_ (NCL) nucleolin at M61764_at (TUBG) gamma M63904_at (GNA15) guanine nucleotide binding protein M64571_at (MAP4) microtubule-associated P4 M68874_at (cPLA2) M76665_at (HSD11) M77836_at pyroline-5-carboxylate reductase M80244_at (SLC7A5) M80563_at (S100A4) M81181_s_at (ATP1B2) M86752_at (IEF SSP 3521) M88458_at M91670_at (E2-EPF) ubiquitin carrier protein E2 M94856_at (FABP5) M95610_at (COL9A2) S81914_at (DIF2) differentiation dependent gene 2 S85655_at (PHB) prohibitin

8 U00238_rna1_a (PPAT) t U02556_at (RP3) candidate gene U03057_at (SNL) U03100_at (CTNNA1) (102kDa) U04636_rna1_a (hCox-2) t U05861_at (DDH2) U07151_at (ARL3) GTP binding protein U09813_at (P3) U10362_at U12387_s_at (TPMT) U13395_at (HHCMA56) U16954_at (AF1q) U17886_at (sdhB) U19261_at EBV-induced protein U19523_at (GCH1) U23942_at (CYP51) cytochrome P450, 51 U28386_at (KPNA2) U30255_at (PGD) U30521_at (p311) U46023_at U49278_at (UBE2V2) ubiquitin-conjugating E2 U55206_at (GGH) U61166_at (ITSN) U61538_at calcuim binding protein chp U63824_at (TEAD4) U67963_at (HU-K5) U70660_at (ATOX1) U72661_at (NINJ1) ninjurin 1 U72761_at (KPNB3) beta 3 karyopherin (importin) U75362_at (USP13) U78735-at (ABC3) U81375_at (ENT1) U90907_at U90913_at U91316_at U94747_at (HAN II) U97105_at (DPYSL2) V00594_s_at (MT1L) metallothionein 1L X16396_at (AA -29-315) X52882_at (AA 1-556) X53793_at (ADE2H1) X59543_at (RPM1) X61100_rna1_a (NDUFS1) t X64177_f_at metallothionein X67318_at (CPA1) X79865_at (Mrp17) X92814_at (orf) X95152_rna1_a (brca2)

9 t X99728_at (NDUFV3) Z37986_at phenylalkylamine Z49099_at (SMS)

Decreased Genes

Transcription factors D31716_at (BTEB1) basic transcription element binding protein J04101_at (ETS1) J04513_at (FGF2) growth factor 2 L05072_s_at (IRF1) interferon regulatory factor 1 L11672_r_at (ZNF91) zinc finger protein 91 (HPF7, HTF10) L39059_at transcription factor SL1 M83233_at (TCF12) transcription factor 12 M87503_at ISGF-3-gamma M97935_s_at ISGF-3 M97936_at transcription factor M98833_at (FL1) Friend leukemia virus integration 1 M99701_at (TCEAL1) transcription elongation factor A (SII)-like1 U22431_s_at (HIF1A) hypoxia-inducible factor 1 U31556_at transcription factor U48213_at (DBP) D site of albumin promoter binding protein U49020_cds2_ (MEF2A) at U71598_at (zf2) zinc finger protein U73843_at E74-like factor 3 (ELF3) up U75276_s_at (TAF3C) TATA box binding protein (TBP)-associated factor U77413_at O-linked N-acetylglucosamine (GLcNAc) U85430_at isoform of NFATx U87269_at E4F transcription factor 1 X15949_at (IRF2) interferon regulatory factor 2 X52611_s_at transcription factor AP-2 (AA1-437) X53390_s_at upstream binding factor (AA 1-764) X59871_at (TCF7) transcription factor 7 (T-cell specific, HMG-box) X60787_s_at interleukin enhancer binding factor 1 X63741_s_at (EGR3) early growth response 3 X66867_cds1_ (MAX) MAX protein at X90824_s_at USF2 upstream transcription factor 2, c-fos interacting X96506_s_at (NC2) alpha subunit; forms heterodimer with NC2 alpha/Dr1 Z22951_rna1_a (p65) t Z36715_at (ELK3) Z47087_at (TCEB1L) transcription elongation factor B (SIII) Z56281_at (IRF3) interferon regulatory factor 3 Receptors/Signaling molecules D00749_s_at (CD7) D10995_at (HTR1B) 5-hydroxytryptamine (serotonin) receptor 1B D38305 _at (TOB) transducer of ERBB2 up

10 D50683_at (TGFBR2) transforming growth factor, beta receptor II J03925_at (ITGAM) integrin, alpha M J04809_rna1_a (AK1) adenylate kinase 1 t K02545_cds2_ (TCRB) +/- 1 bp both ends at L09753_at (CD30L) TNSF8 L14542_at (KLRC4) killer cell lectin-like receptor subfamily C, member 4 L16862_at (GPRK6) -coupled receptor kinase 6 L20688_at (ARHGDIB) GDP dissociation inhibitor up L25851_at (ITGAE) integrin alpha E L29376_at MHC class I cell surface antigen L42324_at (GPCR) L48728_cds1_a (TCRBV10S1) alternative splice product t M12886_at (TCRB) T-cell receptor, beta cluster M12959_at (TCRA) T-cell receptor alpha chain up M15395_at (ITGB2) integrin, beta 2 (antigen CD18) M21624_at (TCRD) T-cell receptor, delta (V,D,J,C) M25280_at (LNHR) lymph node homing receptor precursor M28170_at (CD19) M28879_at granzyme B M29696_at (IL7R) interleukin 7 receptor up M31210_at (EDG1) endothelial differentiation M33195_at (FCER1G) Fc fragment of IgE, high affinity I M36118_s_at (GZMB) granzyme B M37271_s_at (CD7) M54992_at (CD72) M58286_s_at (TNFRSF1A) tumor necrosis factor receptor down superfamily M59829 HSP70-HOM M61906_at P13-kinase, tyrosine M63928_at (TNFRSF7) tumor necrosis factor receptor superfamily down M68941_at (PTPN4) protein tyrosine phosphatase, non-receptor type 4 M69238_at (ARNT) aryl hydrocarbon receptor nuclear translocator M81695_s_at (ITGAX) M88282_at tactile protein, T-cell activation M89957_at (CD79B) CD79B antigen (immunoglobulin-associated beta) M93221_at (MRC1) , C type 1 M93425_at (PTPN12) protein tyrosine phosphatase U00672_at (IL10RA) interleukin 10 receptor, alpha down U04806_s_at FLT3/FLK2 ligand U04898_at (RORA) RAR-related orphan receptor A U05875_at second chain of the receptor U12255_at (FCGRT) Fc fragment of IgG, receptor, transporter, alpha U19487_at (PTGER2) prostaglandin E receptor 2 (subtype EP2), 53kD U32324_at (IL11RA) interleukin 11 receptor, alpha U32674_s_at (GPR9) orphan receptor similar to the interleukin 8 receptors U35735 _at (RACH1) up U42031_at (FKBP5) FK506-binding protein 5 U60975_at (SORL1) sortilin-related receptor, L(DLR class) A

11 U64871_at (GPR19) intronless gene; putative G protein-coupled receptor U66059_cds7_ (TRY3) putative at U68019_ at (MADH3) SMAD3 U89922_ at (LTB) Lymphotoxin beta down U95626_rna1_a () t X00437_s_at T-cell receptor beta-chain X03066_at (HLA-DOB) MHC, class II, DO beta X03663_at (CSF1R) colony stimulating factor 1 receptor X03934_at (CD3D) CD3D antigen, delta polypeptide (TiT3 complex) X04145_at (CD3G) CD3G antigen, gamma polypeptide (TiT3 complex) X07203_at CD20 receptor (AA 1 - 297) X07979_at (ITGB1) down X12530_s_at (CD20) CD20 (AA1-297) X13444_at (CD8B1) CD 8 beta X14046_at (CD37) X16983_at (ITGA4) integrin, alpha 4 (antigen CD49D) up X54870_at (NKG2-D gene) Type II integral X56841_at (HLA-E) X59303_s_at (G7a) MHC, valyl-tRNA synthetase X60922_at (CD6) X62055_at (PTPN6) protein tyrosine phosphatase, non-receptor type 6 X62466_at (CDW52) X64072_at (CD18) X66945_at (N-sam) X69398_at (CD47) CD47 antigen X69819_at (ICAM3) X76223_at (MAL) T-cell differentiation protein up X76648_at (GLRX) glutaredoxin up X76732_at (NUCB2) nucleobindin 2 down X81882_at (CUL5) cullin 5 X84373_at (NRIP1) nuclear receptor interacting protein 1 X94232_at (RP1) T-cell activation protein X95876_at (GPR9) G protein-coupled receptor 9 X97267_rna1_a (CD45) t Y00062_at (PTPRC) protein tyrosine phosphatase, receptor type Y00796_at (ITGAL) Y07827_s_at putative B7, 3 molecule of CD80-CD86 family Z17227_at (IL10RB) interleukin 10 receptor, beta Z22534_at (ACVR1) activin A receptor, type I Z30426_at CD69 early activation antigen Z48541_at (PTPRO) protein tyrosine phosphatase, receptor type, O Kinases/Phosphatases AC002073_at (WUGSC:DJ515N1.2) Putative gene D43636_at (KIAA0096) KIAA0096 D45906_at (LIMK2) LIM domain kinase 2 D63479_s_at (DGKD) diacylglycerol kinase, delta (130kD) J04430_s_at (ACP5) 5, tartrate resistant J04809_rna1_a (AK1) adenylate kinase 1

12 t L01087_at (PRKCQ) , theta L05148_at TCR binding, ZAP-70 protein tyrosine kinase L10717_at 2024-2555 unique domain; 2556-2708 SH3 domain L13738_ at (ACK) syk tyrosine kinase down L16862_at (GPRK6) G protein-coupled receptor kinase 6 L27071_at (TXK) TXK tyrosine kinase L42373_at (PPP2R5A) , regulatory subunit B M14676_at (FYN) FYN oncogene related to SRC, FGR, YES M16591_at (HCK) hematopoetic kinase down M18255_cds2_ (PRKACB) at M34181_at (PRKACB) protein kinase, cAMP-dependent, catalytic, beta M55284_at (PRKCL) M61906_at P13-kinase; tyrosine kinase receptor M68941_at (PTPN4) protein tyrosine phosphatase, non-receptor type 4 M80335_at (PRKACA) protein kinase, cAMP-dependent, catalytic, alpha M93425_at (PTPN12) protein tyrosine phosphatase S75168_rna1_a (Matk) megakaryocyte-associated tyrosine kinase t S78798_s_at 1-phosphatidylinositol-4-phosphate 5-kinase isoform C S81916_at (PGK1) phosphoglycerate kinase 1 U03858_at (FLT3LG) fms-related tyrosine kinase 3 ligand down U23852_s_at (lck) truncated form of p56lck down U33052_s_at (PRKCL2) protein kinase C-like 2 U33841_at (ATM) U48251_at PKC binding protein RACK1 U51477_at (DGKZ) diacylglycerol kinase, zeta (104kD) U57650_at (INPP5D) inositol polyphosphate-5-phosphatase, 145kD U66464_at (HPK1) serine/threonine protein kinase U89896_at CK I gamma 2 X02596_at (BCR) breakpoint cluster region X06318_at (PRKCB1) protein kinase C, beta 1 up X07109_at PKC beta 2 (partial (AA 1-673) X57206_at (ITPKB) inositol 1,4,5-trisphosphate 3-kinase B X62055_at (PTPN6) protein tyrosine phosphatase, non-receptor type 6 X62535_at (DGKA) diacylglycerol kinase, alpha (80kD) X66945_at (N-sam) X78342_at (CDK10) cyclin-dependent kinase (CDC2-like) 10 down up X80497_at (PHKA2) , alpha 2 (liver) X85545_at (PRKX) protein kinase, X-linked X97335_at kinase A anchor protein Y00062_at (PTPRC) protein tyrosine phosphatase, receptor type Y09216_at (DYRK2) dual-specificity regulated kinase 2 Y10032_at () Y11215_at (SKAP55) src kinase-associated phosphoprotein of 55 kDa Z22534_at (ACVR1) activin A receptor, type I Z29090_at (PIK3CA) phosphatidylinositol 3-kinase, catalytic Z35102_at Ndr protein kinase Z48541_at (PTPRO) protein tyrosine phosphatase, receptor type, O Z69881_at x (PTPRO) protein tyrosine phosphatase, receptor type, O

13 Cytokines/interleukins/oncogenes D11086_at (IL2RG) interleukin 2 receptor, gamma up D49950_at (IL18) interleukin 18 D50925_at (KIAA0135) Gene is related to pim-1 oncogene. J03069_rna1_a (MYCL2) v-myc avian myelocytomatosis viral oncogene t L35263_at (CSBP1) Csaids binding protein up L42243_at (IFNAR2) interferon alpha receptor 2 M11313_at (A2M) alpha-2-macroglobulin M14676_at (FYN) FYN oncogene related to SRC, FGR, YES M19722_at (FGR) Gardner-Rasheed feline sarcoma viral (v-fgr) M29696_at (IL7R) interleukin 7 receptor up M69203_at (SCYA2) small inducible cytokine A2 M90391_s_at (IL16) interleukin 16 (lymphocyte chemoattractant factor) M91083_at (C11ORF13) open reading frame 13 U00672_at (IL10RA) interleukin 10 receptor, alpha down U20657_at (USP4) ubiquitin specific protease 4 (proto-oncogene) U32324_at (IL11RA) interleukin 11 receptor, alpha U32674_s_at (GPR9) V01512_rna1_a (FOS) v-fos FBJ murine osteosarcoma viral oncogene t X02596_at (BCR) breakpoint cluster region X16316_at (VAV1) vav 1 oncogene X17576_at (NCK1) NCK adaptor protein 1 X58377_at (IL11) interleukin 11 X60787_at (ILF1) interleukin enhancer binding factor 1 X63546_at (HRP1) hyperpolymorphic gene 1 X66087_at (MYBL1) v-myb avian myeloblastosis viral oncogene X78686_at (SCYB5) small inducible cytokine subfamily B X95876_at (GPR9) G protein-coupled receptor 9 Z17227_at (IL10RB) interleukin 10 receptor, beta Cell cycle/apoptosis/repair AF006041_at (DAXX) death-associated protein D14533_at (XPA) xeroderma pigmentosum complementation group A D38122_at (TNFSF6) tumor necrosis factor (ligand) superfamily D85423_at (CDC5L) CDC5 (cell division cycle 5, S. pombe, homolog) L29217_at (CLK3) CDC-like kinase 3 up M92287 cyclin D3 down S78187_at (CDC25B) cell division cycle 25B up U18291_at (CDC16) cell division cycle 16 U19251_s_at (NAIP) neuronal apoptosis inhibitory protein U20536_s_at (CASP6) caspase 6, apoptosis-related cysteine protease U28014_at (CASP4) caspase 4, apoptosis-related cysteine up protease U40343_at (p19) cyclin-dependent kinase inhibitor, inhibits CDK4 up U47077_at (DNA PKcs) DNA-activated kinase, catalytic polypeptide up U53174_at (RAD9) U61981_at (hMSH3) putative mismatch repair binding protein X05908_at (ANX1) annexin 1 X07024_at CCG1 protein (AA 1 - 1554) X61123_at (BTG1) B-cell translocation gene 1, anti-proliferative

14 X69978_at (ERCC5) X78342_at cyclin-dependent kinase (CDC2-like) 10 X82554_rna1_a (SPHAR) cyclin-related gene t X98172_at (CASP8) caspase 8, apoptosis-related cysteine protease X98176_at MACH-beta 1, cell death protease Miscellaneous AB000464_at Huntington's Disease AB001325_at (AQP3) aquaporin 3 AC000064_cds (PEX1) 2_at AF002020_at (NPC1) putative integral membrane protein AF008937_at (STX16) syntaxin 16 AF009301_at (TEB4) D13631_s_at (KIAA0006) D13641_at (KIAA0016) D14686_at (AMT) aminomethyltransferase D14874_at (ADM) adrenomedulin D16227_at (HPCAL1) hippocalcin-like 1 D16688_s_at (MLLT3) D25304_at (KIAA0006) D26069_at (KIAA0041) D29642_at (KIAA0053) D30756_at (KIAA0049) D30758_at (KIAA0050) D31763_at (KIAA0065) D31846_at (AQP2) aquaporin 2 D31883_at (LIMAB1) limatin D32001_at (HuSAA1g) serum amyloid A1 gamma D38524_at 5' D38535_at (ITIH4) inter-alpha inhibitor H4 D38552_at (KIAA0073) D42053_at (S1P) site 1-protease D50640_at (PDE3B) phospodiesterase 3B D50918_at (KIAA0128) D50927_at (KIAA0137) D50928_at (KIAA1038) D63998_at (MANA2) mannosidase, alpha type II D64015_at (TIAL1) D80010_at (KIAA0188) D83018_at (NRP2) nel-related protein 2 D83735_at (CNN2) calporin 2 D83776_at (KIAA1091) D83782_at (KIAA0199) D86958_at (KIAA0103) D86974_at (KIAA0220) D86976_at (KIAA0223) D87119_at (GS395S) D87436_at (KIAA0249) D87447_at (KIAA0258) D87465_at (KIAA0275)

15 D87683_at (TSC1) D87845_at (PAFAH2) platelet-activating factor acetylhydrolase 2 D90097_at (AMY2B) alpha-amylase HG2238-HT2321_s_at HG2480- HT2576_at HG2868-HT3012_s_at HG2915-HT3059_f_at HG2917-HT3061_f_at HG2981-HT3127_s_at HG3104- HT3280_at HG3115- HT3291_at HG3162- HT3339_at HG3484-HT3678_s_at HG3492- HT3686_at HG3578- HT3781_at HG4036- HT4306_at HG4126- HT4396_at HG4263- HT4533_at HG4390- HT4660_at HG4557- HT4962_at HG4557-HT4962_r_at HG67- HT67_f_at HG998- HT998_s_at J03077_s_at (PSAP) J03801_f_at (LYZ) J04029_s_at (KRT10) J05070_at (MMP9) metalloprotein L04510_at (ARFD1) L05779_at (EPHX2)eposide 2 L07807_s_at (DMN1) dynamin 1 L13852_at (UBE1L) ubiquitin-activating enzyme E1 L16896_at zinc finger protein L19493_s_at (FMR1) L22343_at interferon-induced nuclear phosphoprotein L34657_at (PECAM1) L42621_at (LY9) M11718_at (COL5A2) M13792_at (ADA)

16 M14758_at (PGY1) colchicine resistance (MDR1) M19045_f_at (LYZ) M20867_s_at (GLUD1) M31520_rna1_ (RPS24) at M34516_r_at omega protein M36284_s_at (GYPC) M38591_at (S100A10) M55067_at (NCF1) M55267_at (EVI2A) M55422_at (H-plk) M55543_at (GBP2) M55621_at (MGAT1) M58297_at (ZNF42) M58378_cds1_ (SYN1) at M58600_rna1_ (HCF2) at M60091_at (GALT) M60830_at orf M61916_at (LAMB1) lamin beta 1 M62397_at (MCC) mutated in colorectal cancer M62403_s_at (IGFBP4) M62994_at (FLNB) 1 M63138_at (CTSD) cathepsin D M63904_at (GNA15) guanine nucleotide binding protein M67468_s_at (FMR1) M74715_s_at (IDUA) M85169_at (PSCD1) pleckstrin homology M88458_at M91438_at (HUSI-II) serine proteinase inhibitor M91585_at (BR140) M95678_at (PLCB2) C, beta 2 M96803_at (SPTBN1) beta M97287_at (SATB1) MAR/SAR DNA binding protein S41458_at (PDE6B) S66431_at (RBBP2) Rb binding protein 2 S69272_s_at (PI6) S73591_at (VDUPI) U01317_cds4_ (HBD) at U04241_at (AES) U05259_rna1_a (MB-1) t U07802_at U08377_at (SFRS8) splicing factor U09196_at U09284_at (LIMS1) PINCH protein U12897_at (IPW) U14588_at (PXN) paxillin U17838_at (RIZ)

17 U19713_s_at (IRT-1) interferon gamma responsive transcript U20499_at (SULT1A3) U20758_rna1_a (SPP1) t U20938_at dihydropyrimidine dehydrogenase U26710_at (CBLB) U29607_at methionine aminopeptidase U33429_at (KCNAB2) U37122_at (ADD3) adducin gamma subunit U49835_s_at (CHI3L2) U51587_at (GOLGA1) U52112_rna1_a (RENBP) renin-binding protein t U58516_at (BA46) U61167_at (SH3D1B) U62317_rna3_a (ECGF1) t U64105_at (SUB1.5) U64675_at (BS-63) U67369_at (GFI1) U68142_at (RGL2) U69645_at zinc finger protein U78095_at bikunin U78190_rna1_a (GCHFR) t U79255_at U81556_at U84011_s_at (AGL) U89336_cds1_ (HBX2) at U89336_cds3_ (HBX2) at U89336_cds6_ (HBX2) at U90546_at (BTF4) butyrophilin U90546_r_at (BTF4) butyrophilin U90552_at (BTF5) butyrophilin U90552_s_at (BTF5) butyrophilin U90902_at U90916_at U91932_at (CLAPS3) U93049_at (FYB) FYN-binding protein U95740_rna1_a (A-362G6.1) t U96113_at (WWP1) U97502_rna1_a (BT3.3) butryophilin t V00563_at X04011_at (CYBB) cytochrome b-245, beta X04412_at (GSN) X07290_at (HF.12)

18 X13956_at (AA 1-82) 9kDa protein X14008_rna1_a t X14813_at (ACAA) X16281 (ZNF44) X16282_at (217 AA) X55740_at (NT5) X56687_s_at NOR-90 autoantigen X57351_at (1-8D) X57809_at X59244_f_at (ZNF43) X59834_at (GLUL) X60708_at (DPP4) X63679_at (TRAM) X65644_at (MBP-2) MHC binding protein 2 X67098_at (ORF1) X69111_at (ID3) X69433_at (IDH2) X69910_at (p63) X69962_s_at Fragil X syndrome X72790_at (ORF) X73358_s_at (AES-1) X76061_at (p130) X76534_at (NMB) X78817_at (ARHGAP4) p115 X78924_at (HZF1) zinc finger protein X78992_at (ERF-2) X89109_s_at X89750_at (TGIF) X91809_at (GAIP) X91911_s_at (rtvp-1) X95735_at (ZYX) zyxin X96719_at (CLECSF2) C-type lectin X98411_at (MYO1E) -1E X99209_at arginine methyltransferase Y08682_rna1_a (CPT1B) t Y09392_s_at (wsl-I) WSL-S2 protein Y13618_at (USP9Y) Z21507_at (EEF1D) guanine-nucleotide exchange factor Z35227_at (ARHH) Z36531_at fibrinogen-like protein Z48633_at retrotransposon Z67743_at (CLCN7) chloride channel CLC-7 Z69030_s_at gamma isoform of 61kDa regulatory subunit of PP2A Z94753_s_at (ATP7A) aThe array analysis by Ng et al. (26) could not be included since accession numbers were not published in this study. Harhaj et al. (21); de La Fuente et al. (22); Ruckes et al. (24).

19 20