TY - JOUR
T1 - Genomic analyses identify molecular subtypes of pancreatic cancer
AU - Australian Pancreatic Cancer Genome Initiative
AU - Bailey, Peter
AU - Chang, David K.
AU - Nones, Katia
AU - Johns, Amber L.
AU - Patch, Ann Marie
AU - Gingras, Marie Claude
AU - Miller, David K.
AU - Christ, Angelika N.
AU - Bruxner, Tim J.C.
AU - Quinn, Michael C.
AU - Nourse, Craig
AU - Murtaugh, L. Charles
AU - Harliwong, Ivon
AU - Idrisoglu, Senel
AU - Manning, Suzanne
AU - Nourbakhsh, Ehsan
AU - Wani, Shivangi
AU - Fink, Lynn
AU - Holmes, Oliver
AU - Chin, Venessa
AU - Anderson, Matthew J.
AU - Kazakoff, Stephen
AU - Leonard, Conrad
AU - Newell, Felicity
AU - Waddell, Nick
AU - Wood, Scott
AU - Xu, Qinying
AU - Wilson, Peter J.
AU - Cloonan, Nicole
AU - Kassahn, Karin S.
AU - Taylor, Darrin
AU - Quek, Kelly
AU - Robertson, Alan
AU - Pantano, Lorena
AU - Mincarelli, Laura
AU - Sanchez, Luis N.
AU - Evers, Lisa
AU - Wu, Jianmin
AU - Pinese, Mark
AU - Cowley, Mark J.
AU - Jones, Marc D.
AU - Colvin, Emily K.
AU - Nagrial, Adnan M.
AU - Humphrey, Emily S.
AU - Chantrill, Lorraine A.
AU - Mawson, Amanda
AU - Iacobuzio-Donahue, Christine A.
AU - Wolfgang, Christopher L.
AU - Eshleman, James R.
AU - Hruban, Ralph H.
N1 - Publisher Copyright:
© 2016 Macmillan Publishers Limited. All rights reserved.
PY - 2016/3/3
Y1 - 2016/3/3
N2 - 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.
AB - 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.
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U2 - 10.1038/nature16965
DO - 10.1038/nature16965
M3 - Article
C2 - 26909576
AN - SCOPUS:84960194345
SN - 0028-0836
VL - 531
SP - 47
EP - 52
JO - Nature
JF - Nature
IS - 7592
ER -