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. 2016 Mar 3;531(7592):47-52.
doi: 10.1038/nature16965. Epub 2016 Feb 24.

Genomic Analyses Identify Molecular Subtypes of Pancreatic Cancer

Peter Bailey  1   2 David K Chang  2   3   4   5 Katia Nones  1   6 Amber L Johns  3 Ann-Marie Patch  1   6 Marie-Claude Gingras  7   8   9 David K Miller  1   3 Angelika N Christ  1 Tim J C Bruxner  1 Michael C Quinn  1   6 Craig Nourse  1   2 L Charles Murtaugh  10 Ivon Harliwong  1 Senel Idrisoglu  1 Suzanne Manning  1 Ehsan Nourbakhsh  1 Shivangi Wani  1   6 Lynn Fink  1 Oliver Holmes  1   6 Venessa Chin  3 Matthew J Anderson  1 Stephen Kazakoff  1   6 Conrad Leonard  1   6 Felicity Newell  1 Nick Waddell  1 Scott Wood  1   6 Qinying Xu  1   6 Peter J Wilson  1 Nicole Cloonan  1   6 Karin S Kassahn  1   11   12 Darrin Taylor  1 Kelly Quek  1 Alan Robertson  1 Lorena Pantano  13 Laura Mincarelli  2 Luis N Sanchez  2 Lisa Evers  2 Jianmin Wu  3 Mark Pinese  3 Mark J Cowley  3 Marc D Jones  2   3 Emily K Colvin  3 Adnan M Nagrial  3 Emily S Humphrey  3 Lorraine A Chantrill  3   14 Amanda Mawson  3 Jeremy Humphris  3 Angela Chou  3   15 Marina Pajic  3   16 Christopher J Scarlett  3   17 Andreia V Pinho  3 Marc Giry-Laterriere  3 Ilse Rooman  3 Jaswinder S Samra  18   19 James G Kench  3   19   20 Jessica A Lovell  3 Neil D Merrett  5   21 Christopher W Toon  3 Krishna Epari  22 Nam Q Nguyen  23 Andrew Barbour  24 Nikolajs Zeps  25 Kim Moran-Jones  2 Nigel B Jamieson  2   26   27 Janet S Graham  2   28 Fraser Duthie  29 Karin Oien  3   29 Jane Hair  30 Robert Grützmann  31 Anirban Maitra  32 Christine A Iacobuzio-Donahue  33 Christopher L Wolfgang  34   35 Richard A Morgan  34 Rita T Lawlor  36   37 Vincenzo Corbo  36 Claudio Bassi  38 Borislav Rusev  36 Paola Capelli  37 Roberto Salvia  38 Giampaolo Tortora  39 Debabrata Mukhopadhyay  40 Gloria M Petersen  40 Australian Pancreatic Cancer Genome InitiativeDonna M Munzy  7   8 William E Fisher  41 Saadia A Karim  42 James R Eshleman  34 Ralph H Hruban  34 Christian Pilarsky  31 Jennifer P Morton  42 Owen J Sansom  42   43 Aldo Scarpa  36   37 Elizabeth A Musgrove  2 Ulla-Maja Hagbo Bailey  2 Oliver Hofmann  2   13 Robert L Sutherland  3 David A Wheeler  7   8 Anthony J Gill  3   19 Richard A Gibbs  7   8 John V Pearson  1   6 Nicola Waddell  1   6 Andrew V Biankin  2   3   4   5   27 Sean M Grimmond  1   2   44
Collaborators, Affiliations

Genomic Analyses Identify Molecular Subtypes of Pancreatic Cancer

Peter Bailey et al. Nature. .

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.

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