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

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..

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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.