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Genomic analyses identify molecular subtypes of pancreatic cancer
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...
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Published in: | Nature (London) 2016-03, Vol.531 (7592), p.47-52 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
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Summary: | 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.
An integrated genomic analysis of 456 human pancreatic ductal adenocarcinomas identifies four subtypes defined by transcriptional expression profiles and show that these are associated with distinct histopathological characteristics and differential prognosis.
Pancreatic cancer genomics
Sean Grimmond and colleagues report integrated genomic analysis of 456 pancreatic ductal adenocarcinomas. They identify four subtypes defined by expression profiles, characterize their transcriptional networks, and show that these are associated with distinct histopathological characteristics and differential survival. |
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ISSN: | 0028-0836 1476-4687 |
DOI: | 10.1038/nature16965 |