Mutations of isocitrate dehydrogenase 1 and 2 in intrahepatic cholangiocarcinoma.

Abstract:

PURPOSE OF REVIEW:Exome sequencing studies have recently expanded the genetic characterization of intrahepatic cholangiocarcinomas. Among a number of novel genes, isocitrate dehydrogenase (IDH) is recurrently mutated in intrahepatic cholangiocarcinomas. We review the effects of these mutations on several biochemical pathways, as well as potential changes to downstream signaling pathways. RECENT FINDINGS:Hotspot mutations in IDH isoforms 1 or 2 occur in approximately 15% of intrahepatic cholangiocarcinomas. These mutations result in elevated levels of an oncometabolite, 2-hydroxyglutarate, which is associated with higher DNA CpG methylation and altered histone methylation that accompany a block in cellular differentiation. Exploratory studies have suggested additional phenotypes associated with IDH1/2 mutations. SUMMARY:Tumors with IDH1 or IDH2 mutations may represent a distinct subtype of cholangiocarcinomas. Further studies are required to elucidate the exact role that mutant IDH1/2 and 2-hydroxyglutarate play in tumorigenesis, and what are the best strategies to target these tumor types.

authors

Grassian AR,Pagliarini R,Chiang DY

doi

10.1097/MOG.0000000000000050

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

295-302

issue

3

eissn

0267-1379

issn

1531-7056

journal_volume

30

pub_type

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