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 abstractGrants
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 Academy of Medical Sciences (AMS)
Awarded by Cancer Research UK
Awarded by Medical Research Council
Awarded by Versus Arthritis
Awarded by Wellcome Trust
Awarded by Pancreatic Cancer UK
Awarded by NATIONAL CANCER INSTITUTE
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.