View Item 

Genomic analyses identify molecular subtypes of pancreatic cancer

Access Status
Fulltext not available
Authors
Bailey, P.
Chang, D.
Nones, K.
Johns, A.
Patch, A.
Gingras, M.
Miller, D.
Christ, A.
Bruxner, T.
Quinn, M.
Nourse, C.
Murtaugh, L.
Harliwong, I.
Idrisoglu, S.
Manning, S.
Nourbakhsh, E.
Wani, S.
Fink, L.
Holmes, O.
Chin, V.
Anderson, M.
Kazakoff, S.
Leonard, C.
Newell, F.
Waddell, N.
Wood, S.
Xu, Q.
Wilson, P.
Cloonan, N.
Kassahn, K.
Taylor, D.
Quek, K.
Robertson, A.
Pantano, L.
Mincarelli, L.
Sanchez, L.
Evers, L.
Wu, J.
Pinese, M.
Cowley, M.
Jones, M.
Colvin, E.
Nagrial, A.
Humphrey, E.
Chantrill, L.
Mawson, A.
Humphris, J.
Chou, A.
Pajic, M.
Scarlett, C.
Pinho, A.
Giry-Laterriere, M.
Rooman, I.
Samra, J.
Kench, J.
Lovell, J.
Merrett, N.
Toon, C.
Epari, K.
Nguyen, N.
Barbour, A.
Zeps, Nikolajs
Moran-Jones, K.
Jamieson, N.
Graham, J.
Duthie, F.
Oien, K.
Hair, J.
Gruetzmann, R.
Maitra, A.
Iacobuzio-Donahue, C.
Wolfgang, C.
Morgan, R.
Lawlor, R.
Corbo, V.
Bassi, C.
Rusev, B.
Capelli, P.
Salvia, R.
Tortora, G.
Mukhopadhyay, D.
Petersen, G.
Munzy, D.
Fisher, W.
Karim, S.
Eshleman, J.
Hruban, R.
Pilarsky, C.
Morton, J.
Sansom, O.
Scarpa, A.
Musgrove, E.
Bailey, U.
Hofmann, O.
Sutherland, R.
Wheeler, D.
Gill, A.
Gibbs, R.
Pearson, J.
Waddell, N.
Biankin, A.
Grimmond, S.
Date
2016
Type
Journal Article

Metadata
Show full item record
Citation
Bailey, P. and Chang, D. and Nones, K. and Johns, A. and Patch, A. and Gingras, M. and Miller, D. et al. 2016. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 531 (7592): pp. 47-52.
Source Title
Nature
DOI
ISSN
URI
Collection
Abstract

© 2016 Macmillan Publishers Limited. All rights reserved.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 TP63ΔN 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.