Genomic analyses identify molecular subtypes of pancreatic cancer

Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJC, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grützmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JR, Sansom OJ, Scarpa A, Musgrove EA, Bailey UMH, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM, Pilarsky C (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 531

Pages Range: 47-52

Journal Issue: 7592

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-?, 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.

Authors with CRIS profile

Involved external institutions

Kinghorn Cancer Centre Australia (AU) Royal North Shore Hospital (RNSH) Australia (AU) University of New South Wales (UNSW) Australia (AU) Houston Texas Medical Center United States (USA) (US) University of Queensland Australia (AU) University of Glasgow United Kingdom (GB) University of Utah United States (USA) (US) Harvard University United States (USA) (US) Fiona Stanley Hospital Australia (AU) Royal Adelaide Hospital Australia (AU) Princess Alexandra Hospital Australia (AU) University of Western Australia (UWA) Australia (AU) NHS Greater Glasgow and Clyde United Kingdom (GB) University of Texas Medical Branch (UTMB) United States (USA) (US) Memorial Sloan Kettering Cancer Center United States (USA) (US) Johns Hopkins University (JHU) United States (USA) (US) University Hospital of Verona / Azienda Ospedaliera Universitaria Integrata Verona (AOUI) Italy (IT) University of Verona / Università degli Studi di Verona Italy (IT) Mayo Clinic United States (USA) (US) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Technische Universität Dresden Germany (DE)

How to cite

APA:

Bailey, P., Chang, D.K., Nones, K., Johns, A.L., Patch, A.-M., Gingras, M.-C.,... Pilarsky, C. (2016). Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 531(7592), 47-52. https://dx.doi.org/10.1038/nature16965

MLA:

Bailey, Peter, et al. "Genomic analyses identify molecular subtypes of pancreatic cancer." Nature 531.7592 (2016): 47-52.

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