Journal
NATURE GENETICS
Volume 45, Issue 12, Pages 1470-U93Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2813
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Funding
- D.K. Ludwig Fund for Cancer Research
- Lustgarten Foundation for Pancreatic Cancer Research
- US National Institutes of Health (NIH) [P50 CA62924, K08DK090154, EDRN U01CA086402]
- Associazione Italiana Ricerca Cancro (AIRC) [12182, 11930, 6421, IG 12214]
- Italian Cancer Genome Project [FIRB RBAP10AHJB]
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Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.
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