| Literature DB >> 26909576 |
Peter Bailey1,2, David K Chang2,3,4,5, Katia Nones1,6, Amber L Johns3, Ann-Marie Patch1,6, Marie-Claude Gingras7,8,9, David K Miller1,3, Angelika N Christ1, Tim J C Bruxner1, Michael C Quinn1,6, Craig Nourse1,2, L Charles Murtaugh10, Ivon Harliwong1, Senel Idrisoglu1, Suzanne Manning1, Ehsan Nourbakhsh1, Shivangi Wani1,6, Lynn Fink1, Oliver Holmes1,6, Venessa Chin3, Matthew J Anderson1, Stephen Kazakoff1,6, Conrad Leonard1,6, Felicity Newell1, Nick Waddell1, Scott Wood1,6, Qinying Xu1,6, Peter J Wilson1, Nicole Cloonan1,6, Karin S Kassahn1,11,12, Darrin Taylor1, Kelly Quek1, Alan Robertson1, Lorena Pantano13, Laura Mincarelli2, Luis N Sanchez2, Lisa Evers2, Jianmin Wu3, Mark Pinese3, Mark J Cowley3, Marc D Jones2,3, Emily K Colvin3, Adnan M Nagrial3, Emily S Humphrey3, Lorraine A Chantrill3,14, Amanda Mawson3, Jeremy Humphris3, Angela Chou3,15, Marina Pajic3,16, Christopher J Scarlett3,17, Andreia V Pinho3, Marc Giry-Laterriere3, Ilse Rooman3, Jaswinder S Samra18,19, James G Kench3,19,20, Jessica A Lovell3, Neil D Merrett5,21, Christopher W Toon3, Krishna Epari22, Nam Q Nguyen23, Andrew Barbour24, Nikolajs Zeps25, Kim Moran-Jones2, Nigel B Jamieson2,26,27, Janet S Graham2,28, Fraser Duthie29, Karin Oien3,29, Jane Hair30, Robert Grützmann31, Anirban Maitra32, Christine A Iacobuzio-Donahue33, Christopher L Wolfgang34,35, Richard A Morgan34, Rita T Lawlor36,37, Vincenzo Corbo36, Claudio Bassi38, Borislav Rusev36, Paola Capelli37, Roberto Salvia38, Giampaolo Tortora39, Debabrata Mukhopadhyay40, Gloria M Petersen40, Donna M Munzy7,8, William E Fisher41, Saadia A Karim42, James R Eshleman34, Ralph H Hruban34, Christian Pilarsky31, Jennifer P Morton42, Owen J Sansom42,43, Aldo Scarpa36,37, Elizabeth A Musgrove2, Ulla-Maja Hagbo Bailey2, Oliver Hofmann2,13, Robert L Sutherland3, David A Wheeler7,8, Anthony J Gill3,19, Richard A Gibbs7,8, John V Pearson1,6, Nicola Waddell1,6, Andrew V Biankin2,3,4,5,27, Sean M Grimmond1,2,44.
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. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.Entities:
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Year: 2016 PMID： 26909576 DOI： 10.1038/nature16965
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962