Genomic analyses identify molecular subtypes of pancreatic cancer

Baile, Peter, Chang, David K., Nones, Katia, Johns, Amber L., Patch, Ann-Marie, Gingras, Marie-Claude, Miller, David K., Christ, Angelika N., Bruxner, Tim J. C., Quinn, Michael C., Nourse, Craig, Murtaugh, L. Charles, Harliwong, Ivon, Idrisoglu, Senel, Manning, Suzanne, Nourbakhsh, Ehsan, Wani, Shivangi, Fink, Lynn, Holmes, Oliver, Chin, Vencssa, Anderson, Matthew J., Kazakoff, Stephen, Leonard, Conrad, Newell, Felicity, Waddell, Nick, Wood, Scott, Xu, Qinying, Wilson, Peter J., Cloonan, Nicole, Kassahn, Karin S., Taylor, Darrin, Quek, Kelly, Robertson, Alan, Pantano, Lorena, Mincarelli, Laura, Sanchez, Luis N., Evers, Lisa, Wu, Jianmin, Pinese, Mark, Cowley, Mark J., Jones, Marc D., Colvin, Emily K., Nagrial, Adnan M., Humphrey, Emily S., Chantrill, Lorraine A., Mawson, Amanda, Humphris, Jeremy, Chou, Angela, Pajic, Marina, Scarlett, Christopher J., Pinho, Andreia V., Giry-Laterriere, Marc, Rooman, Ilse, Samra, Jaswinder S., Kench, James G., Lovell, Jessica A., Merrett, Neil D., Toon, Christopher W., Epari, Krishna, Nguyen, Nam Q., Barbour, Andrew, Zeps, Nikolajs, Moran-Jones, Kim, Jamieson, Nigel B., Graham, Janet S., Duthie, Fraser, Oien, Karin, Hair, Jane, Gruetzmann, Robert, Maitra, Anirban, Iacobuzio-Donahue, Christine A., Wolfgang, Christopher L., Morgan, Richard A., Lawlor, Rita T., Corbo, Vincenzo, Bassi, Claudio, Rusev, Borislav, Capelli, Paola, Salvia, Roberto, Tortora, Giampaolo, Mukhopadhyay, Debabrata, Petersen, Gloria M., Munzy, Donna M., Fisher, William E., Karim, Saadia A., Eshleman, James R., Hruban, Ralph H., Pilarsky, Christian, Morton, Jennifer R., Sansom, Owen J., Scarpa, Aldo, Musgrove, Elizabeth A., Bailey, Ulla-Maja Hagbo, Hofmann, Oliver, Sutherland, Robert L., Wheeler, David A., Gill, Anthony J., Gibbs, Richard A., Pearson, John V., Waddell, Nicola, Biankin, Andrew V. and Grimmond, Sean M. (2016) Genomic analyses identify molecular subtypes of pancreatic cancer. Nature, 531 7592: 47-52. doi:10.1038/nature16965


Author Baile, Peter
Chang, David K.
Nones, Katia
Johns, Amber L.
Patch, Ann-Marie
Gingras, Marie-Claude
Miller, David K.
Christ, Angelika N.
Bruxner, Tim J. C.
Quinn, Michael C.
Nourse, Craig
Murtaugh, L. Charles
Harliwong, Ivon
Idrisoglu, Senel
Manning, Suzanne
Nourbakhsh, Ehsan
Wani, Shivangi
Fink, Lynn
Holmes, Oliver
Chin, Vencssa
Anderson, Matthew J.
Kazakoff, Stephen
Leonard, Conrad
Newell, Felicity
Waddell, Nick
Wood, Scott
Xu, Qinying
Wilson, Peter J.
Cloonan, Nicole
Kassahn, Karin S.
Taylor, Darrin
Quek, Kelly
Robertson, Alan
Pantano, Lorena
Mincarelli, Laura
Sanchez, Luis N.
Evers, Lisa
Wu, Jianmin
Pinese, Mark
Cowley, Mark J.
Jones, Marc D.
Colvin, Emily K.
Nagrial, Adnan M.
Humphrey, Emily S.
Chantrill, Lorraine A.
Mawson, Amanda
Humphris, Jeremy
Chou, Angela
Pajic, Marina
Scarlett, Christopher J.
Pinho, Andreia V.
Giry-Laterriere, Marc
Rooman, Ilse
Samra, Jaswinder S.
Kench, James G.
Lovell, Jessica A.
Merrett, Neil D.
Toon, Christopher W.
Epari, Krishna
Nguyen, Nam Q.
Barbour, Andrew
Zeps, Nikolajs
Moran-Jones, Kim
Jamieson, Nigel B.
Graham, Janet S.
Duthie, Fraser
Oien, Karin
Hair, Jane
Gruetzmann, Robert
Maitra, Anirban
Iacobuzio-Donahue, Christine A.
Wolfgang, Christopher L.
Morgan, Richard A.
Lawlor, Rita T.
Corbo, Vincenzo
Bassi, Claudio
Rusev, Borislav
Capelli, Paola
Salvia, Roberto
Tortora, Giampaolo
Mukhopadhyay, Debabrata
Petersen, Gloria M.
Munzy, Donna M.
Fisher, William E.
Karim, Saadia A.
Eshleman, James R.
Hruban, Ralph H.
Pilarsky, Christian
Morton, Jennifer R.
Sansom, Owen J.
Scarpa, Aldo
Musgrove, Elizabeth A.
Bailey, Ulla-Maja Hagbo
Hofmann, Oliver
Sutherland, Robert L.
Wheeler, David A.
Gill, Anthony J.
Gibbs, Richard A.
Pearson, John V.
Waddell, Nicola
Biankin, Andrew V.
Grimmond, Sean M.
Title Genomic analyses identify molecular subtypes of pancreatic cancer
Journal name Nature   Check publisher's open access policy
ISSN 1476-4687
0028-0836
Publication date 2016-03-03
Year available 2016
Sub-type Article (original research)
DOI 10.1038/nature16965
Open Access Status Not yet assessed
Volume 531
Issue 7592
Start page 47
End page 52
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Formatted 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 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.
Keyword Integrated genomic analysis
Pancreatic ductal adenocarcinomas
Carcinomas
Squamous tumours
Acquired immune suppression
Immunogenic tumours
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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