Genomic analyses identify molecular subtypes of pancreatic cancer
Date
2016
Authors
Bailey, P.
Chang, D.
Nones, K.
Johns, A.
Patch, A.
Gingras, M.
Miller, D.
Christ, A.
Bruxner, T.
Quinn, M.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Nature, 2016; 531(7592):47-52
Statement of Responsibility
Peter Bailey, David K. Chang, Katia Nones, Amber L. Johns, Ann-Marie Patch, Marie-Claude Gingras, David K. Miller, Angelika N. Christ, Tim J. C. Bruxner, Michael C. Quinn, Craig Nourse, L. Charles Murtaugh, Ivon Harliwong, Senel Idrisoglu, Suzanne Manning, Ehsan Nourbakhsh, Shivangi Wani, Lynn Fink, Oliver Holmes, Venessa Chin, Matthew J. Anderson, Stephen Kazakoff, Conrad Leonard, Felicity Newell, Nick Waddell, Scott Wood, Qinying Xu, Peter J. Wilson, Nicole Cloonan, Karin S. Kassahn, Darrin Taylor, Kelly Quek, Alan Robertson, Lorena Pantano, Laura Mincarelli, Luis N. Sanchez, Lisa Evers, Jianmin Wu, Mark Pinese, Mark J. Cowley, Marc D. Jones, Emily K. Colvin, Adnan M. Nagrial, Emily S. Humphrey, Lorraine A. Chantrill, Amanda Mawson, Jeremy Humphris, Angela Chou, Marina Pajic, Christopher J. Scarlett, Andreia V. Pinho, Marc Giry-Laterriere, Ilse Rooman, Jaswinder S. Samra, James G. Kench, Jessica A. Lovell, Neil D. Merrett, Christopher W. Toon, Krishna Epari, Nam Q. Nguyen, Andrew Barbour, Nikolajs Zeps, Kim Moran-Jones, Nigel B. Jamieson, Janet S. Graham, Fraser Duthie, Karin Oien, Jane Hair, Robert Grützmann, Anirban Maitra, Christine A. Iacobuzio-Donahue, Christopher L. Wolfgang, Richard A. Morgan, Rita T. Lawlor, Vincenzo Corbo, Claudio Bassi, Borislav Rusev, Paola Capelli, Roberto Salvia, Giampaolo Tortora, Debabrata Mukhopadhyay, Gloria M. Petersen, Australian Pancreatic Cancer Genome Initiative, Donna M. Munzy, William E. Fisher, Saadia A. Karim, James R. Eshleman, Ralph H. Hruban, Christian Pilarsky, Jennifer P. Morton, Owen J. Sansom, Aldo Scarpa, Elizabeth A. Musgrove, Ulla-Maja Hagbo Bailey, Oliver Hofmann, Robert L. Sutherland, David A. Wheeler, Anthony J. Gill, Richard A. Gibbs, John V. Pearson, Nicola Waddell, Andrew V. Biankin, Sean M. Grimmond
Conference Name
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.
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
© 2016 Macmillan Publishers Limited. All rights reserved.