Table S1 Primers used for genomic DNA sequencing of K-Ras and TP53

Gene, exon Forward primer Reverse primer k-Ras, exon 1 GTTCTAATATAGTCACATTT ACTCATGAAAATGGTCAGAGAAACCTTTAT k-Ras, exon 2 GAAGTAAAAGGTGCACTGTA AACTATAATTACTCCTTAAT

TP53, exon 4 AGGACCTGGTCCTCTGAC CTGGGAAGGGACAGAAGA

TP53, exon 5 TGACTTTCAACTCTGTCTCCT TCAGTGAGGAATCAGAGGCC

TP53, exon 6 CTGGAGAGACGACAGAGGCC CCAGAGACCCCAGTTGCAAAC

TP53, exon 7 AAGGCGCACTGGCCTCATCTT CGCCGGAAATGTGATGAGAG

TP53, exon 8 TGGTTGGGAGTAGATGGAGCC CACCGCTTCTTGTCCTGCTT

TP53, exon 9 GTGGAGGAGACCAAGGGTGCA AGGTAAAACAGTCAAGAAGAA

Table S2. in cytogenetic band with recurrent copy number alterations Gains

Cytoband name Cytoband Gene Protein name 1 q42.2 KIAA1383 KIAA1383 18 q11.1-11.2 KIAA1772 KIAA1772 establishment of cohesion 1 homolog 1 (S. 1 q42.2 C1orf57 1 open reading frame 57 18 q11.1-11.2 ESCO1 cerevisiae) 1 q42.2 PCNXL2 pecanex-like 2 (Drosophila) 18 q11.1-11.2 SNRPD1 small nuclear ribonucleoprotein D1 polypeptide 1 q42.2 KIAA1804 mixed lineage kinase 4 18 q11.1-11.2 ABHD3 abhydrolase domain containing 3 11 q13.1 SLC25A45 solute carrier family 25, member 45 18 q11.1-11.2 MIB1 mindbomb homolog 1 (Drosophila) 11 q13.1 FRMD8 FERM domain containing 8 18 q11.1-11.2 GATA6 GATA binding protein 6 11 q13.1 NCRNA00084 non-protein coding RNA 84 18 q11.1-11.2 CTAGE1 cutaneous T-cell lymphoma-associated antigen 1 metastasis associated lung adenocarcinoma 11 q13.1 MALAT1 18 q11.1-11.2 RBBP8 retinoblastoma binding protein 8 transcript 1 (non-protein coding) 20 q13.13 CEBPB CCAAT/enhancer binding protein (C/EBP), beta Losses

Cytoband Gene Protein name Cytoband Gene Protein name 2 p11.1 LOC654342 lymphocyte-specific protein 1 pseudogene 18 q22.1 CDH7 cadherin 7, type 2 2 p11.1 GGT8P gamma-glutamyltransferase 8 pseudogene 18 q22.1 CDH19 cadherin 19, type 2 9 p21.3 C9orf53 chromosome 9 open reading frame 53 18 q22.1 DSEL dermatan sulfate epimerase-like cyclin-dependent kinase inhibitor 2A 9 p21.3 CDKN2A 18 q22.1 TMX3 thioredoxin-related transmembrane protein 3 (melanoma, p16, inhibits CDK4) cyclin-dependent kinase inhibitor 2B (p15, CCDC102 9 p21.3 CDKN2B 18 q22.1 coiled-coil domain containing 102B inhibits CDK4) B CDKN2BA CDKN2B antisense RNA (non-protein 9 p21.3 18 q22.3-23 FBXO15 F-box protein 15 S coding) 9 p21.3 DMRTA1 DMRT-like family A1 18 q22.3-23 C18orf55 open reading frame 55 ELAV (embryonic lethal, abnormal vision, 9 p21.3 ELAVL2 18 q22.3-23 CYB5A cytochrome b5 type A (microsomal) Drosophila)-like 2 (Hu antigen B) family with sequence similarity 95, member 9 p11.2 FAM95B1 18 q22.3-23 C18orf51 chromosome 18 open reading frame 51 B1 ANKRD20 9 p11.2 ankyrin repeat domain 20 family, member A3 18 q22.3-23 CPGL carboxypeptidase of glutamate-like A3 ANKRD20 carnosine dipeptidase 1 (metallopeptidase M20 9 p11.2 ankyrin repeat domain 20 family, member A2 18 q22.3-23 CNDP1 A2 family) family with sequence similarity 75, member LOC40065 9 p11.2 FAM75A6 18 q22.3-23 hypothetical LOC400657 A6 7 9 p11.2 KGFLP1 keratinocyte growth factor-like protein 1 18 q22.3-23 ZNF407 zinc finger protein 407 family with sequence similarity 27, member zinc binding alcohol dehydrogenase domain 9 p11.2 FAM27C 18 q22.3-23 ZADH2 C containing 2 10 q11.22 PPYR1 pancreatic polypeptide receptor 1 18 q22.3-23 TSHZ1 teashirt zinc finger homeobox 1 heterogeneous nuclear ribonucleoprotein A1 10 q11.22 LOC728643 18 q22.3-23 C18orf62 chromosome 18 open reading frame 62 pseudogene 10 q11.22 ANXA8L1 annexin A8-like 1 18 q22.3-23 ZNF516 zinc finger protein 516 10 q11.22 ANXA8 annexin A8 18 q22.3-23 GALR1 galanin receptor 1 family with sequence similarity 25, member 10 q11.22 FAM25B 18 q22.3-23 SALL3 C2H2 zinc finger protein SALL3 B family with sequence similarity 25, member 10 q11.22 FAM25C 18 q22.3-23 ATP9B ATPase, class II, type 9B C family with sequence similarity 25, member nuclear factor of activated T-cells, cytoplasmic, 10 q11.22 FAM25G 18 q22.3-23 NFATC1 G calcineurin-dependent 1 CTD (carboxy-terminal domain, RNA polymerase II, 10 q11.22 LOC642826 hypothetical LOC642826 18 q22.3-23 CTDP1 polypeptide A) phosphatase, subunit 1 olfactory receptor, family 11, subfamily H, potassium voltage-gated channel, subfamily G, 14 q11.1-11.2 OR11H12 18 q22.3-23 KCNG2 member 1 member 2 14 q11.1-11.2 POTEG POTE ankyrin domain family, member G 18 q22.3-23 PQLC1 PQ loop repeat containing 1 LOC44049 14 q11.1-11.2 P704P prostate-specific P704P 18 q22.3-23 heat shock factor binding protein 1-like 8 olfactory receptor, family 4, subfamily Q, 14 q11.1-11.2 OR4Q3 18 q22.3-23 TXNL4A thioredoxin-like 4A member 3 olfactory receptor, family 4, subfamily M, 14 q11.1-11.2 OR4M1 18 q22.3-23 C18orf22 chromosome 18 open reading frame 22 member 1 olfactory receptor, family 4, subfamily N, 14 q11.1-11.2 OR4N2 18 q22.3-23 ADNP2 ADNP homeobox 2 member 2 olfactory receptor, family 4, subfamily K, LOC10013 14 q11.1-11.2 OR4K2 18 q22.3-23 similar to hCG1996578 member 2 0522 olfactory receptor, family 4, subfamily K, par-6 partitioning defective 6 homolog gamma (C. 14 q11.1-11.2 OR4K5 18 q22.3-23 PARD6G member 5 elegans) olfactory receptor, family 4, subfamily K, 14 q11.1-11.2 OR4K1 19 q13.31 PSG1 pregnancy specific beta-1-glycoprotein 1 member 1 15 q11.1-11.2 LOC727832 golgi autoantigen, golgin subfamily a-like 19 q13.31 PSG6 pregnancy specific beta-1-glycoprotein 6 15 q11.1-11.2 GOLGA8C golgi autoantigen, golgin subfamily a, 8C 19 q13.31 PSG7 pregnancy specific beta-1-glycoprotein 7 15 q11.1-11.2 LOC646214 p21-activated kinase 2 pseudogene 19 q13.31 PSG11 pregnancy specific beta-1-glycoprotein 11 coxsackie virus and adenovirus receptor 15 q11.1-11.2 CXADRP2 19 q13.31 PSG2 pregnancy specific beta-1-glycoprotein 2 pseudogene 2 15 q11.1-11.2 POTEB POTE ankyrin domain family, member B 20 q11.1 FRG1B FSHD region gene 1 family, member B 15 q11.1-11.2 LOC727924 hypothetical LOC727924 21 p11.2-11.1 TPTE transmembrane phosphatase with tensin homology olfactory receptor, family 4, subfamily M, 15 q11.1-11.2 OR4M2 21 p11.2-11.1 BAGE2 B melanoma antigen family, member 2 member 2 olfactory receptor, family 4, subfamily N, 15 q11.1-11.2 OR4N4 21 p11.2-11.1 BAGE3 B melanoma antigen family, member 3 member 4 15 q11.1-11.2 LOC650137 seven transmembrane helix receptor 21 p11.2-11.1 BAGE4 B melanoma antigen family, member 4 18 q12.2 KIAA1328 KIAA1328 21 p11.2-11.1 BAGE5 B melanoma antigen family, member 5 18 q12.2 BRUNOL4 bruno-like 4, RNA binding protein 21 p11.2-11.1 BAGE B melanoma antigen serpin peptidase inhibitor, clade B 18 q21.33 SERPINB4 22 q13.31 GRAMD4 GRAM domain containing 4 (ovalbumin), member 4 serpin peptidase inhibitor, clade B 18 q21.33 SERPINB3 22 q13.31 CERK ceramide kinase (ovalbumin), member 3 serpin peptidase inhibitor, clade B TBC1D22 18 q21.33 SERPINB11 22 q13.31 TBC1 domain family, member 22A (ovalbumin), member 11 (gene/pseudogene) A serpin peptidase inhibitor, clade B 18 q21.33 SERPINB7 (ovalbumin), member 7

Table S3. Genes with high copy number gain.

Sample cytoband Gene Name Molecular Function Other Aliases sema domain, transmembrane domain VIA, SEMA, HT018, protein binding, receptor Panc-13 5q23.1 SEMA6A (TM), and cytoplasmic domain, SEMAQ, SEMA6A1, activity (semaphorin) 6A KIAA1368 sequence-specific DNA OTF3C, OTF3P1, Panc-23 8q24.21 POU5F1P1 POU class 5 homeobox 1B binding, transcription POU5F1P1, POU5FLC8 factor activity LOC727677 hypothetical LOC727677 MYC c-myc protein L15, RAMA3, NY-REN- Panc-8 11p14.1 CCDC34 coiled-coil domain containing 34 41 protein binding, protein- leucine-rich repeat-containing G protein- LGR4 hormone receptor activity, GPR48 coupled receptor 4 receptor activity MALS3, VELI3, LIN-7C, LIN7C lin-7 homolog C (C. Elegans) protein binding MALS-3, LIN-7-C, FLJ11215 BT2A, BT2B, BT2C, BDNF opposite strand (non-protein BDNFOS BT2D, ANTI-BDNF, coding) NCRNA00049 translation initiation factor A121, ISO1, SUI1, EIF-1, Panc-33 17q21.2 EIF1 eukaryotic translation initiation factor 1 activity EIF1A hormone activity, protein GAST gastrin GAS binding HAP1 -associated protein 1 HLP, HAP2, HIP5, hHLP1 cytoskeletal protein DP3, PDGB, PKGB, JUP junction plakoglobin binding, protein CTNNG, DPIII, ARVD12 phosphatase binding SC65 synaptonemal complex protein SC65 NOL55 calcium ion binding, FKBP6, FKBP65, isomerase activity, FKBP10 FK506 binding protein 10, 65 kDa hFKBP65, FLJ20683, peptidyl-prolyl cis-trans FLJ22041, FLJ23833 isomerase activity A log2 ratio >2.0 was regarded as high copy number gain. Note that this study identified four patients, each carrying copy number gain of one of the four cytobands.

Table S4. Association of 18q22.3 loss with clinicopathological parameters in the Korean cohort.

18q22.3 18q22.3 Characteristic Subcategory p-value Normal loss age(year) ≦65.5 17 5 0.70 >65.5 19 3 gender male 22 4 0.70 female 14 4 tumor size ≦2cm 5 1 1 >2cm 31 7 lymph node negative 18 0 0.03 positive 18 7 unknown 0 1 Stage (AJCC) I-IIA 19 0 0.007 IIB 17 7 III 0 1 grade I-II 28 6 1 III 5 1 unknown 3 1 angiolymphatic invasion negative 21 2 0.13 positive 15 6 venous invasion negative 28 4 0.19 positive 8 4 perineural invasion negative 11 1 0.41 positive 25 7 adjuvant therapy no 13 6 0.11 yes 22 2 unknown 1 0 Table S5. Genes in cytogenetic band 18q22.3.

Gene Name Molecular Function Other Aliases FBXO15 F-box protein 15 protein binding FBX15, MGC39671 chromosome 18 open C18orf55 HSPC154 reading frame 55 cytochrome b5 type A aldo-keto reductase activity, cytochrome-c oxidase activity, CYB5A CYB5, MCB5 (microsomal) heme binding, metal ion binding chromosome 18 open C18orf51 reading frame 51 carboxypeptidase activity, dipeptidase activity, metal ion CN2, CNDP2, Carboxypeptidase of CPGL binding, metallopeptidase activity, peptidase activity, protein PEPA, HsT2298, glutamate like dimerization activity, zinc ion binding FLJ10830

Table S6.Array-based comparative genomic hybridization analyses on pancreatic cancer

cell Resolution micro- Survival Functional First author tumors xenograftsa Reference lines (probes) array analysis analysisb Aguirre 24 13 0 14160 yes no - (1) Heidenblad 31 0 0 3565/25648c no no - (2) Holzmann 13 6 0 812d no no - (3) Mahlamaki 13 0 0 12232 yes no - (4) Bashyam 22 0 0 39632 yes no - (5) Gysin 25 0 0 2464 yes no - (6) Nowak 16 0 17 ~5400 no no - (7) Calhoun 26 0 0 115,353 no no - (8) Loukopoulos 0 33 11 800d yes yes - (9) Harada 0 27 0 116,000 no no - (10) Kimmelman 15 14 0 ~43,000 no no RIOK3/PAK4 (11) Kwei 0 0 31 39,632 yese no GATA6 (12) Suzuki 24 0 0 800d no no SMURF1 (13) Birnbaum 8 39 0 225,388 no no - (14) Present study 0 44 0 ~105,000 no yes CPGL/CPGL-B a. xenografts were established from primary tumor for enrichment of cancer cells b. knocking-down or overexpression of selected genes c. two platforms d. selected known cancer related genes only e. microarray on chromosome 18 only

Figure S1. Confirmation of the copy number by real-time PCR assay in 25 Korean tumors.

(A) Relationship between copy number of the CPGL gene determined by aCGH assay and by real-time PCR assay. (B) Relationship between the copy number of the CPGL gene and the

FBXO15 gene. The results of aCGH assay and of real-time PCR are presented as delta log2 ratio and delta Ct value, respectively, between the CPGL gene and the RPPH1 gene. Each point represents individual sample.

Figure S2. Kaplan-Meier survival curve of the Italian cohort stratified by mutation status of (A) the Kras gene and (B) the TP53 gene. Solid lines: wild-type, dashed lines: mutant.

Comparison of survival probabilities over time was determined by log-rank test. Tick marks on the survival curves indicate censored data points.

Figure S3. CPGL Knockdown in the PANC-1 cell. (A) Real-time RT-PCR on mRNA expression of the CPGL and CPGL-B in cells transfected with control or CPGL siRNA. (B)

CPGL protein expression in cells transfected with control or CPGL siRNA. (C) Proliferation assay of cells transfected with siRNA. (D) Cell cycle analyses. (E) Wound healing assay. Data were collected at 0hr and 16hr after wounding. References:

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