Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma

Cancer Cell - Tập 32 Số 2 - Trang 185-203.e13 - 2017
Benjamin J. Raphael, Ralph H. Hruban, Andrew J. Aguirre, Richard A. Moffitt, Jen Jen Yeh, Chip Stewart, A. Gordon Robertson, Andrew D. Cherniack, Manaswi Gupta, Gad Getz, Stacey Gabriel, Matthew Meyerson, Carrie Cibulskis, Suzanne S. Fei, Toshinori Hinoue, Hui Shen, Peter W. Laird, Shiyun Ling, Yiling Lu, Gordon B. Mills, Rehan Akbani, Phillipe Loher, Eric Londin, Isidore Rigoutsos, Aristeidis G. Telonis, Ewan A. Gibb, Anna Goldenberg, Aziz M. Mezlini, Katherine A. Hoadley, Eric A. Collisson, Sı́lvia Beà, Bradley A. Murray, Julian M. Hess, Mara Rosenberg, Louis Bergelson, Hailei Zhang, Juok Cho, Grace Tiao, Jaegil Kim, Dimitri Livitz, Ignaty Leshchiner, Brendan Reardon, Eliezer M. Van Allen, Atanas Kamburov, Rameen Beroukhim, Gordon Saksena, Steven E. Schumacher, Michael S. Noble, David I. Heiman, Nils Gehlenborg, Michael S. Lawrence, Volkan Adsay, Gloria M. Petersen, David S. Klimstra, Nabeel Bardeesy, Mark D.M. Leiserson, Reanne Bowlby, Katayoon Kasaian, İnanç Birol, Andrew J. Mungall, Sara Sadeghi, John N. Weinstein, Paul T. Spellman, Yuexin Liu, Laufey T. Ámundadóttir, Joel E. Tepper, Aatur D. Singhi, Rajiv Dhir, Paul Drwiega, Thomas C. Smyrk, Lizhi Zhang, Paula Kim, Jay Bowen, Jessica Frick, Julie M. Gastier‐Foster, Mark Gerken, Kevin Lau, Kristen Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Jeremy Renkel, Mark E. Sherman, Lisa Wise, Peggy Yena, Erik Zmuda, Juliann Shih, Adrian Ally, Miruna Balasundaram, Rebecca Carlsen, Andy Chu, Eric Chuah, Amanda Clarke, Noreen Dhalla, Robert A. Holt, Steven J.M. Jones, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Denise Brooks, J. Todd Auman, Saianand Balu, Tom Bodenheimer, D. Neil Hayes, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Charles M. Perou, Amy H. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Joel S. Parker, Matthew D. Wilkerson, Anil Korkut, Yasin Şenbabaoğlu, Patrick A. Burch, Robert R. McWilliams, Kari G. Rabe, Ann L. Oberg, Wei Zhang, Marie‐Claude Gingras, David A. Wheeler, Xi Liu, Monique Albert, John M.S. Bartlett, Harman Sekhon, Yeager Stephen, Zoë Howard, Judy Miller, Anne Breggia, Rachna T. Shroff, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Smith Jennifer, Kevin K. Roggin, Karl‐Friedrich Becker, Madhusmita Behera, Joseph Bennett, Lori Boice, Eric Burks, Carlos Gilberto Carlotti, John A. Chabot, Daniela Pretti da Cunha Tirapelli, José Sebastião dos Santos, Michael Dubina, Jennifer Eschbacher, Mei Huang, Lori Huelsenbeck-Dill, Roger Jenkins, А. А. Карпов, Rafael Kemp, Vladimir Lyadov, Shishir K. Maithel, Georgy M. Manikhas, Eric Montgomery, Houtan Noushmehr, Adeboye O. Osunkoya, Taofeek K. Owonikoko, Oxana Paklina, Olga Potapova, Suresh Ramalingam, W. Kimryn Rathmell, Kimberly Rieger‐Christ, Charles Saller, Galiya Setdikova, Shabunin Av, Gabriel L. Sica, Tao Su, Travis Sullivan, Pat Swanson, Katherine Tarvin, Mikhail Tavobilov, Leigh B. Thorne, Stefan J. Urbanski, Olga Voronina, Timothy C. Wang, Daniel Crain, Erin Curley, Johanna Gardner, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Klaus‐Peter Janssen, Oliver F. Bathe, Nathan Bahary, Julia Slotta‐Huspenina, Amber L. Johns, Hanina Hibshoosh, Rosa F. Hwang, Antonia R. Sepulveda, Amie Radenbaugh, Stephen B. Baylin, Mario Berríos, Moiz S. Bootwalla, Andrea Holbrook, Phillip H. Lai, Dennis T. Maglinte, Swapna Mahurkar‐Joshi, Tim Triche, David J. Van Den Berg, Daniel J. Weisenberger, Lynda Chin, Raju Kucherlapati, Melanie H. Kucherlapati, Angeliki Pantazi, Peter J. Park, Doug Voet, Pei Lin, Scott Frazer, Timothy Defreitas, Sam Meier, Sun Young Kwon, Yong‐Hoon Kim, Sang‐Jae Park, Sung‐Sik Han, Seong Hoon Kim, Hark Kyun Kim, Emma E. Furth, Margaret A. Tempero, Chris Sander, Andrew V. Biankin, David K. Chang, Peter J. Allen, Anthony J. Gill, James G. Kench, Sean M. Grimmond, Australian Pancreatic Cancer Genome Initiative APGI, Russell G. Postier, Rosemary E. Zuna, Hugues Sicotte, John A. Demchok, Martin L. Ferguson, Carolyn M. Hutter, Kenna Shaw, Margi Sheth, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jiashan Zhang, Ina Felau, Jean C. Zenklusen

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Tài liệu tham khảo

Agarwal, 2015, Predicting effective microRNA target sites in mammalian mRNAs, Elife, 4, 10.7554/eLife.05005

Akbani, 2014, A pan-cancer proteomic perspective on The Cancer Genome Atlas, Nat. Commun., 5, 3887, 10.1038/ncomms4887

Alexandrov, 2013, Signatures of mutational processes in human cancer, Nature, 500, 415, 10.1038/nature12477

Amato, 2014, Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas, J. Pathol., 233, 217, 10.1002/path.4344

Bailey, 2016, Genomic analyses identify molecular subtypes of pancreatic cancer, Nature, 531, 47, 10.1038/nature16965

Berger, 2012, Melanoma genome sequencing reveals frequent PREX2 mutations, Nature, 485, 502, 10.1038/nature11071

Biankin, 2012, Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes, Nature, 491, 399, 10.1038/nature11547

Bibikova, 2011, High density DNA methylation array with single CpG site resolution, Genomics, 98, 288, 10.1016/j.ygeno.2011.07.007

Bibikova, 2009, Genome-wide DNA methylation profiling using Infinium(R) assay, Epigenomics, 1, 177, 10.2217/epi.09.14

Campan, 2009, MethyLight, Methods Mol. Biol., 507, 325, 10.1007/978-1-59745-522-0_23

Cancer Genome Atlas Network, 2012, Comprehensive molecular portraits of human breast tumours, Nature, 490, 61, 10.1038/nature11412

Cancer Genome Atlas Research Network, 2014, Integrated genomic characterization of papillary thyroid carcinoma, Cell, 159, 676, 10.1016/j.cell.2014.09.050

Carter, 2012, Absolute quantification of somatic DNA alterations in human cancer, Nat. Biotechnol., 30, 413, 10.1038/nbt.2203

Chatterjee, 2015, Caveolin-1 is associated with tumor progression and confers a multi-modality resistance phenotype in pancreatic cancer, Sci. Rep., 5, 10867, 10.1038/srep10867

Chen, 2016, Oncogenic BRAF deletions that function as homodimers and are sensitive to inhibition by RAF dimer inhibitor LY3009120, Cancer Discov., 6, 300, 10.1158/2159-8290.CD-15-0896

Chou, 2016, miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database, Nucleic Acids Res., 44, D239, 10.1093/nar/gkv1258

Chou, 2016, IRAK1, a target of miR-146b, reduces cell aggressiveness of human papillary thyroid carcinoma, J. Clin. Endocrinol. Metab., 101, 4357, 10.1210/jc.2016-2276

Chu, 2016, Large-scale profiling of microRNAs for The Cancer Genome Atlas, Nucleic Acids Res., 44, e3, 10.1093/nar/gkv808

Cibulskis, 2011, ContEst: estimating cross-contamination of human samples in next-generation sequencing data, Bioinformatics, 27, 2601, 10.1093/bioinformatics/btr446

Cibulskis, 2013, Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples, Nat. Biotechnol., 31, 213, 10.1038/nbt.2514

Clark, 2014, Argonaute CLIP-Seq reveals miRNA targetome diversity across tissue types, Sci. Rep., 4, 5947, 10.1038/srep05947

Collisson, 2011, Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy, Nat. Med., 17, 500, 10.1038/nm.2344

Costello, 2012, Evidence for changes in RREB-1, ZIP3, and Zinc in the early development of pancreatic adenocarcinoma, J. Gastrointest. Cancer, 43, 570, 10.1007/s12029-012-9378-1

Costello, 2013, Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation, Nucleic Acids Res., 41, e67, 10.1093/nar/gks1443

Dobin, 2013, STAR: ultrafast universal RNA-seq aligner, Bioinformatics, 29, 15, 10.1093/bioinformatics/bts635

Dulak, 2013, Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity, Nat. Genet., 45, 478, 10.1038/ng.2591

Ehrlich, 2002, Hypomethylation and hypermethylation of DNA in Wilms tumors, Oncogene, 21, 6694, 10.1038/sj.onc.1205890

Fan, 2016, Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway, Biochem. Biophys. Res. Commun., 474, 660, 10.1016/j.bbrc.2016.04.146

Fernandez-Cabezudo, 2016, Deficiency of mitochondrial modulator MCJ promotes chemoresistance in breast cancer, JCI Insight, 1, 10.1172/jci.insight.86873

Fisher, 2011, A scalable, fully automated process for construction of sequence-ready human exome targeted capture libraries, Genome Biol., 12, R1, 10.1186/gb-2011-12-1-r1

Flex, 2008, Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia, J. Exp. Med., 205, 751, 10.1084/jem.20072182

Foster, 2016, Activation mechanism of oncogenic deletion mutations in BRAF, EGFR, and HER2, Cancer Cell, 29, 477, 10.1016/j.ccell.2016.02.010

Frampton, 2015, microRNAs with prognostic significance in pancreatic ductal adenocarcinoma: a meta-analysis, Eur. J. Cancer, 51, 1389, 10.1016/j.ejca.2015.04.006

Franklin, 2014, The cytotoxic role of RREB1, ZIP3 zinc transporter, and zinc in human pancreatic adenocarcinoma, Cancer Biol. Ther., 15, 1431, 10.4161/cbt.29927

Fu, 2008, Frequent genomic copy number gain and overexpression of GATA-6 in pancreatic carcinoma, Cancer Biol. Ther., 7, 1593, 10.4161/cbt.7.10.6565

Gaujoux, 2010, A flexible R package for nonnegative matrix factorization, BMC Bioinformatics, 11, 367, 10.1186/1471-2105-11-367

Gibb, 2015, Activation of an endogenous retrovirus-associated long non-coding RNA in human adenocarcinoma, Genome Med., 7, 22, 10.1186/s13073-015-0142-6

Goggins, 1996, Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas, Cancer Res., 56, 5360

Gonzalez-Angulo, 2011, Functional proteomics can define prognosis and predict pathologic complete response in patients with breast cancer, Clin. Proteomics, 8, 11, 10.1186/1559-0275-8-11

Grant, 2015, Prevalence of germline mutations in cancer predisposition genes in patients with pancreatic cancer, Gastroenterology, 148, 556, 10.1053/j.gastro.2014.11.042

Halkova, 2015, MicroRNAs in pancreatic cancer: involvement in carcinogenesis and potential use for diagnosis and prognosis, Gastroenterol. Res. Pract., 2015, 892903, 10.1155/2015/892903

Hao, 2016, NPInter v3.0: an upgraded database of noncoding RNA-associated interactions, Database (Oxford), 2016, 10.1093/database/baw057

He, 2014, 2564 resected periampullary adenocarcinomas at a single institution: trends over three decades, HPB, 16, 83, 10.1111/hpb.12078

Hennessy, 2010, A technical assessment of the utility of reverse phase protein arrays for the study of the functional proteome in non-microdissected human breast cancers, Clin. Proteomics, 6, 129, 10.1007/s12014-010-9055-y

Hernandez, 2016, MicroRNA in pancreatic ductal adenocarcinoma and its precursor lesions, World J. Gastrointest. Oncol., 8, 18, 10.4251/wjgo.v8.i1.18

Honda, 2016, Clinical prognostic value of DNA methylation in hepatoblastoma: four novel tumor suppressor candidates, Cancer Sci., 107, 812, 10.1111/cas.12928

Hsu, 2014, miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions, Nucleic Acids Res., 42, D78, 10.1093/nar/gkt1266

Hu, 2007, Non-parametric quantification of protein lysate arrays, Bioinformatics, 23, 1986, 10.1093/bioinformatics/btm283

Huang da, 2009, Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources, Nat. Protoc., 4, 44, 10.1038/nprot.2008.211

Huang, 2014, Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1), Cell Death Dis., 5, e1008, 10.1038/cddis.2013.541

Huarte, 2015, The emerging role of lncRNAs in cancer, Nat. Med., 21, 1253, 10.1038/nm.3981

Iacobuzio-Donahue, 2002, Exploring the host desmoplastic response to pancreatic carcinoma: gene expression of stromal and neoplastic cells at the site of primary invasion, Am. J. Pathol., 160, 91, 10.1016/S0002-9440(10)64353-2

Iacobuzio-Donahue, 2004, Large-scale allelotype of pancreaticobiliary carcinoma provides quantitative estimates of genome-wide allelic loss, Cancer Res., 64, 871, 10.1158/0008-5472.CAN-03-2756

Izawa, 2001, Clonality and field cancerization in intraductal papillary-mucinous tumors of the pancreas, Cancer, 92, 1807, 10.1002/1097-0142(20011001)92:7<1807::AID-CNCR1697>3.0.CO;2-0

Jeggari, 2012, miRcode: a map of putative microRNA target sites in the long non-coding transcriptome, Bioinformatics, 28, 2062, 10.1093/bioinformatics/bts344

Jiang, 2015, The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression, Cell Rep., 11, 137, 10.1016/j.celrep.2015.03.008

Jiang, 2013, Inactivating mutations of RNF43 confer Wnt dependency in pancreatic ductal adenocarcinoma, Proc. Natl. Acad. Sci. USA, 110, 12649, 10.1073/pnas.1307218110

Jones, 2008, Core signaling pathways in human pancreatic cancers revealed by global genomic analyses, Science, 321, 1801, 10.1126/science.1164368

Ju, 2015, Development of a robust classifier for quality control of reverse-phase protein arrays, Bioinformatics, 31, 912, 10.1093/bioinformatics/btu736

Keim, 2001, Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene, Am. J. Med., 111, 622, 10.1016/S0002-9343(01)00958-5

Kent, 2010, Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway, Genes Dev., 24, 2754, 10.1101/gad.1950610

Kent, 2013, RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targets, Oncogene, 32, 2576, 10.1038/onc.2012.266

Koboldt, 2012, VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing, Genome Res., 22, 568, 10.1101/gr.129684.111

Koo, 2015, Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia, Proc. Natl. Acad. Sci. USA, 112, 7548, 10.1073/pnas.1508113112

Korn, 2008, Integrated genotype calling and association analysis of SNPs, common copy number polymorphisms and rare CNVs, Nat. Genet., 40, 1253, 10.1038/ng.237

Lawrence, 2013, Mutational heterogeneity in cancer and the search for new cancer-associated genes, Nature, 499, 214, 10.1038/nature12213

Lawrence, 2014, Discovery and saturation analysis of cancer genes across 21 tumour types, Nature, 505, 495, 10.1038/nature12912

Le, 2015, PD-1 blockade in tumors with mismatch-repair deficiency, N. Engl. J. Med., 372, 2509, 10.1056/NEJMoa1500596

Lee, 2015, Postoperative prognosis prediction of pancreatic cancer with seven microRNAs, Pancreas, 44, 764, 10.1097/MPA.0000000000000346

Lee, 2016, Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins, Cell, 164, 69, 10.1016/j.cell.2015.12.017

Leiserson, 2015, MAGI: visualization and collaborative annotation of genomic aberrations, Nat. Methods, 12, 483, 10.1038/nmeth.3412

Li, 2011, RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome, BMC Bioinformatics, 12, 323, 10.1186/1471-2105-12-323

Li, 2010, Fast and accurate long-read alignment with Burrows-Wheeler transform, Bioinformatics, 26, 589, 10.1093/bioinformatics/btp698

Li, 2013, Finding consistent patterns: a nonparametric approach for identifying differential expression in RNA-Seq data, Stat. Methods Med. Res., 22, 519, 10.1177/0962280211428386

Li, 2008, Improved correction for population stratification in genome-wide association studies by identifying hidden population structures, Genet. Epidemiol., 32, 215, 10.1002/gepi.20296

Li, 2009, The sequence alignment/map format and SAMtools, Bioinformatics, 25, 2078, 10.1093/bioinformatics/btp352

Li, 2016, Identification of long-non coding RNA UCA1 as an oncogene in renal cell carcinoma, Mol. Med. Rep., 13, 3326, 10.3892/mmr.2016.4894

Liang, 2007, The energy sensing LKB1-AMPK pathway regulates p27(kip1) phosphorylation mediating the decision to enter autophagy or apoptosis, Nat. Cell Biol., 9, 218, 10.1038/ncb1537

Lindsey, 2006, Epigenetic inactivation of MCJ (DNAJD1) in malignant paediatric brain tumours, Int. J. Cancer, 118, 346, 10.1002/ijc.21353

Lito, 2016, Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism, Science, 351, 604, 10.1126/science.aad6204

Lock, 2015, Loss of negative regulators amplifies RAS signaling, Nat. Genet., 47, 426, 10.1038/ng.3299

Loher, 2012, Interactive exploration of RNA22 microRNA target predictions, Bioinformatics, 28, 3322, 10.1093/bioinformatics/bts615

Lohr, 2012, Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing, Proc. Natl. Acad. Sci. USA, 109, 3879, 10.1073/pnas.1121343109

Londin, 2015, Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs, Proc. Natl. Acad. Sci. USA, 112, E1106, 10.1073/pnas.1420955112

Lou, 2013, Pancreatic cancer: modulation of KRAS, MicroRNAs, and intercellular communication in the setting of tumor heterogeneity, Pancreas, 42, 1218, 10.1097/MPA.0000000000000007

Manichaikul, 2010, Robust relationship inference in genome-wide association studies, Bioinformatics, 26, 2867, 10.1093/bioinformatics/btq559

Martinelli, 2016, GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer, Gut

McKenna, 2010, The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data, Genome Res., 20, 1297, 10.1101/gr.107524.110

McLaren, 2016, The ensembl variant effect predictor, Genome Biol., 17, 122, 10.1186/s13059-016-0974-4

Mele, 2017, Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs, Genome Res., 27, 27, 10.1101/gr.214205.116

Mermel, 2011, GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers, Genome Biol., 12, R41, 10.1186/gb-2011-12-4-r41

Miranda, 2006, A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes, Cell, 126, 1203, 10.1016/j.cell.2006.07.031

Moffitt, 2015, Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma, Nat. Genet., 47, 1168, 10.1038/ng.3398

Muller, 2015, Next-generation sequencing reveals novel differentially regulated mRNAs, lncRNAs, miRNAs, sdRNAs and a piRNA in pancreatic cancer, Mol. Cancer, 14, 94, 10.1186/s12943-015-0358-5

Mullokandov, 2012, High-throughput assessment of microRNA activity and function using microRNA sensor and decoy libraries, Nat. Methods, 9, 840, 10.1038/nmeth.2078

Nagpal, 2014, PCMdb: pancreatic cancer methylation database, Sci. Rep., 4, 4197, 10.1038/srep04197

Nguyen, 2016, Expression specificity of disease-associated lncRNAs: toward personalized medicine, Curr. Top. Microbiol. Immunol., 394, 237

Nie, 2016, LncRNA-UCA1 exerts oncogenic functions in non-small cell lung cancer by targeting miR-193a-3p, Cancer Lett., 371, 99, 10.1016/j.canlet.2015.11.024

Notta, 2016, A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns, Nature, 538, 378, 10.1038/nature19823

Ostrem, 2013, K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions, Nature, 503, 548, 10.1038/nature12796

Price, 2006, Principal components analysis corrects for stratification in genome-wide association studies, Nat. Genet., 38, 904, 10.1038/ng1847

Purcell, 2014, A polygenic burden of rare disruptive mutations in schizophrenia, Nature, 506, 185, 10.1038/nature12975

Qi, 2016, PARP6 acts as a tumor suppressor via downregulating Survivin expression in colorectal cancer, Oncotarget, 7, 18812, 10.18632/oncotarget.7712

Quinn, 2016, Unique features of long non-coding RNA biogenesis and function, Nat. Rev. Genet., 17, 47, 10.1038/nrg.2015.10

Rahib, 2014, Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States, Cancer Res., 74, 2913, 10.1158/0008-5472.CAN-14-0155

Ramos, 2015, Oncotator: cancer variant annotation tool, Hum. Mutat., 36, E2423, 10.1002/humu.22771

Rein, 2011, Potential markers for detection and monitoring of ovarian cancer, J. Oncol., 2011, 475983

Roberts, 2016, Whole genome sequencing defines the genetic heterogeneity of familial pancreatic cancer, Cancer Discov., 6, 166, 10.1158/2159-8290.CD-15-0402

Ryan, 2014, Pancreatic adenocarcinoma, N. Engl. J. Med., 371, 1039, 10.1056/NEJMra1404198

Sahin, 2016, Molecular signature of pancreatic adenocarcinoma: an insight from genotype to phenotype and challenges for targeted therapy, Expert Opin. Ther. Targets, 20, 341, 10.1517/14728222.2016.1094057

Sahin, 2016, Genomic instability in pancreatic adenocarcinoma: a new step towards precision medicine and novel therapeutic approaches, Expert Rev. Gastroenterol. Hepatol., 10, 893

Saunders, 2012, Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs, Bioinformatics, 28, 1811, 10.1093/bioinformatics/bts271

Shen, 2012, Integrative subtype discovery in glioblastoma using iCluster, PLoS One, 7, e35236, 10.1371/journal.pone.0035236

Siegel, 2016, Cancer statistics, 2016, CA Cancer J. Clin., 66, 7, 10.3322/caac.21332

Sigova, 2013, Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells, Proc. Natl. Acad. Sci. USA, 110, 2876, 10.1073/pnas.1221904110

Stransky, 2011, The mutational landscape of head and neck squamous cell carcinoma, Science, 333, 1157, 10.1126/science.1208130

Subramanian, 2005, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Proc. Natl. Acad. Sci. USA, 102, 15545, 10.1073/pnas.0506580102

Sun, 2015, MicroRNA signaling pathway network in pancreatic ductal adenocarcinoma, J. Genet. Genomics, 42, 563, 10.1016/j.jgg.2015.07.003

Tan, 2015, GNAS and KRAS mutations define separate progression pathways in intraductal papillary mucinous neoplasm-associated carcinoma, J. Am. Coll. Surg., 220, 845, 10.1016/j.jamcollsurg.2014.11.029

Thorvaldsdottir, 2013, Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration, Brief Bioinform., 14, 178, 10.1093/bib/bbs017

Tibes, 2006, Reverse phase protein array: validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoietic stem cells, Mol. Cancer Ther., 5, 2512, 10.1158/1535-7163.MCT-06-0334

Trapnell, 2010, Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation, Nat. Biotechnol., 28, 511, 10.1038/nbt.1621

Triche, 2013, Low-level processing of illumina infinium DNA methylation beadArrays, Nucleic Acids Res., 41, e90, 10.1093/nar/gkt090

Tusher, 2001, Significance analysis of microarrays applied to the ionizing radiation response, Proc. Natl. Acad. Sci. USA, 98, 5116, 10.1073/pnas.091062498

Van Allen, 2014, Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine, Nat. Med., 20, 682, 10.1038/nm.3559

Waddell, 2015, Whole genomes redefine the mutational landscape of pancreatic cancer, Nature, 518, 495, 10.1038/nature14169

Wang, 2014, Similarity network fusion for aggregating data types on a genomic scale, Nat. Methods, 11, 333, 10.1038/nmeth.2810

Wang, 2008, UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion, FEBS Lett., 582, 1919, 10.1016/j.febslet.2008.05.012

Wang, 2010, MapSplice: accurate mapping of RNA-seq reads for splice junction discovery, Nucleic Acids Res., 38, e178, 10.1093/nar/gkq622

Whitcomb, 1996, Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene, Nat. Genet., 14, 141, 10.1038/ng1096-141

Wilkerson, 2010, ConsensusClusterPlus: a class discovery tool with confidence assessments and item tracking, Bioinformatics, 26, 1572, 10.1093/bioinformatics/btq170

Witkiewicz, 2015, Whole-exome sequencing of pancreatic cancer defines genetic diversity and therapeutic targets, Nat. Commun., 6, 6744, 10.1038/ncomms7744

Wolfgang, 2013, Recent progress in pancreatic cancer, CA Cancer J. Clin., 63, 318, 10.3322/caac.21190

Wood, 2012, Pathology and molecular genetics of pancreatic neoplasms, Cancer J., 18, 492, 10.1097/PPO.0b013e31827459b6

Wu, 2011, Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways, Proc. Natl. Acad. Sci. USA, 108, 21188, 10.1073/pnas.1118046108

Wu, 2011, Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development, Sci. Transl Med., 3, 92ra66, 10.1126/scitranslmed.3002543

Wu, 2015, The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma, Oncotarget, 6, 9160, 10.18632/oncotarget.3247

Xiao, 2014, Zinc-finger protein 545 inhibits cell proliferation as a tumor suppressor through inducing apoptosis and is disrupted by promoter methylation in breast cancer, PLoS One, 9, e110990, 10.1371/journal.pone.0110990

Yang, 2014, Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells, Gut, 63, 881, 10.1136/gutjnl-2013-305266

Yu, 2015, Hypermethylation of ZNF545 is associated with poor prognosis in patients with early-stage hepatocellular carcinoma after thermal ablation, Gut, 64, 1836, 10.1136/gutjnl-2015-310258

Zack, 2013, Pan-cancer patterns of somatic copy number alteration, Nat. Genet., 45, 1134, 10.1038/ng.2760

Zhang, 2009, Serial dilution curve: a new method for analysis of reverse phase protein array data, Bioinformatics, 25, 650, 10.1093/bioinformatics/btn663

Zorn, 2009, Vertebrate endoderm development and organ formation, Annu. Rev. Cell Dev. Biol., 25, 221, 10.1146/annurev.cellbio.042308.113344