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.
journal_name
Curr Opin Gastroenteroljournal_title
Current opinion in gastroenterologyauthors
Grassian AR,Pagliarini R,Chiang DYdoi
10.1097/MOG.0000000000000050subject
Has Abstractpub_date
2014-05-01 00:00:00pages
295-302issue
3eissn
0267-1379issn
1531-7056journal_volume
30pub_type
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journal_title:Current opinion in gastroenterology
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