Genomic analyses identify molecular subtypes of pancreatic cancer

Peter Bailey; David K Chang; Katia Nones; Amber L Johns; Ann-Marie Patch; Marie-Claude Gingras; David K Miller; Angelika N Christ; Tim JC Bruxner; Michael C Quinn; Craig Nourse; L Charles Murtaugh; Ivon Harliwong; Senel Idrisoglu; Suzanne Manning; Ehsan Nourbakhsh; Shivangi Wani; Lynn Fink; Oliver Holmes; Vencssa Chin; Matthew J Anderson; Stephen Kazakoff; Conrad Leonard; Felicity Newell; Nick Waddell; Scott Wood; Qinying Xu; Peter J Wilson; Nicole Cloonan; Karin S Kassahn; Darrin Taylor; Kelly Quek; Alan Robertson; Lorena Pantano; Laura Mincarelli; Luis N Sanchez; Lisa Evers; Jianmin Wu; Mark Pinese; Mark J Cowley; Marc D Jones; Emily K Colvin; Adnan M Nagrial; Emily S Humphrey; Lorraine A Chantrill; Amanda Mawson; Jeremy Humphris; Angela Chou; Marina Pajic; Christopher J Scarlett; Andreia V Pinho; Marc Giry-Laterriere; Ilse Rooman; Jaswinder S Samra; James G Kench; Jessica A Lovell; Neil D Merrett; Christopher W Toon; Krishna Epari; Nam Q Nguyen; Andrew Barbour; Nikolajs Zeps; Kim Moran-Jones; Nigel B Jamieson; Janet S Graham; Fraser Duthie; Karin Oien; Jane Hair; Robert Gruetzmann; Anirban Maitra; Christine A Iacobuzio-Donahue; Christopher L Wolfgang; Richard A Morgan; Rita T Lawlor; Vincenzo Corbo; Claudio Bassi; Borislav Rusev; Paola Capelli; Roberto Salvia; Giampaolo Tortora; Debabrata Mukhopadhyay; Gloria M Petersen; Donna M Munzy; William E Fisher; Saadia A Karim; James R Eshleman; Ralph H Hruban; Christian Pilarsky; Jennifer R Morton; Owen J Sansom; Aldo Scarpa; Elizabeth A Musgrove; Ulla-Maja Hagbo Bailey; Oliver Hofmann; Robert L Sutherland; David A Wheeler; Anthony J Gill; Richard A Gibbs; John V Pearson; Nicola Waddell; Andrew V Biankin; Sean M Grimmond

Journal article

Genomic analyses identify molecular subtypes of pancreatic cancer

Peter Bailey, David K Chang, Katia Nones, Amber L Johns, Ann-Marie Patch, Marie-Claude Gingras, David K Miller, Angelika N Christ, Tim JC Bruxner, Michael C Quinn, Craig Nourse, L Charles Murtaugh, Ivon Harliwong, Senel Idrisoglu, Suzanne Manning, Ehsan Nourbakhsh, Shivangi Wani, Lynn Fink, Oliver Holmes, Vencssa Chin Show all

NATURE | NATURE PUBLISHING GROUP | Published : 2016

DOI: 10.1038/nature16965

Abstract

Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreat..

View full abstract

University of Melbourne Researchers

Oliver Hofmann Author Clinical Pathology

Mehrdad Nikfarjam Author Surgery - Austin Health

Sean Grimmond Author

Related Projects (1)

INTERNATIONAL CANCER GENOME CONSORTIUM

nan

Grants

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by Cancer Council NSW

Awarded by Cancer Institute NSW

Awarded by Cancer Research UK Glasgow Centre Program

Awarded by Wellcome Trust Senior Investigator Award

Awarded by Cancer Research UK Programme Grant

Awarded by European Research Council Starting Grant

Awarded by Italian Ministry of University and Research (Cancer Genome Project)

Awarded by Associazione Italiana Ricerca Cancro

Awarded by Fondazione Italiana Malattie Pancreas - Ministry of Health

Awarded by European Community Grant FP7 Cam-Pac

Awarded by MRC

Awarded by Academy of Medical Sciences (AMS)

Awarded by Cancer Research UK

Awarded by Cancer Research UK; Versus Arthritis

Awarded by Medical Research Council

Awarded by Pancreatic Cancer UK

Awarded by Versus Arthritis; Cancer Research UK

Awarded by Wellcome Trust

Funding Acknowledgements

We would like to thank C. Axford, M.-A. Brancato, S. Rowe, M. Thomas, S. Simpson and G. Hammond for central coordination of the Australian Pancreatic Cancer Genome Initiative, data management and quality control; M. Martyn-Smith, L. Braatvedt, H. Tang, V. Papangelis and M. Beilin for biospecimen acquisition; and Deborah Gwynne for support at the Queensland Centre for Medical Genomics. We also thank M. Hodgins, M. Debeljak and D. Trusty for technical assistance at Johns Hopkins University. Funding support was from: National Health and Medical Research Council of Australia (NHMRC; 631701, 535903, 427601); Queensland Government (NIRAP); University of Queensland; Australian Government: Department of Innovation, Industry, Science and Research (DIISR); Australian Cancer Research Foundation (ACRF); Cancer Council NSW: (SRP06-01, SRP11-01. ICGC); Cancer Institute NSW: (10/ECF/2-26; 06/ECF/1-24; 09/CDF/2-40; 07/CDF/1-03; 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26,10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26); Garvan Institute of Medical Research; Cancer Research UK Glasgow Centre Program, A18076; Avner Nahmani Pancreatic Cancer Research Foundation; R.T. Hall Trust; Petre Foundation; Philip Hemstritch Foundation; Gastroenterological Society of Australia (GESA); American Association for Cancer Research (AACR) Landon Foundation-INNOVATOR Award; Wellcome Trust Senior Investigator Award 103721/Z/14/Z; Cancer Research UK Programme Grant C29717/A17263; Cancer Research UK Programme Grant A12481; Pancreatic Cancer UK; The Howat Foundation; University of Glasgow; European Research Council Starting Grant, 311301, Italian Ministry of University and Research (Cancer Genome Project FIRB RBAP10AHJB), Associazione Italiana Ricerca Cancro (n. 12182), Fondazione Italiana Malattie Pancreas - Ministry of Health (CUP_J33G13000210001), European Community Grant FP7 Cam-Pac, grant agreement number 602783.