Mutations in IDH1/2 Seen in Intrahepatic Bile Duct Cancers

Mutations found in about a quarter of cholangiocarcinomas of intrahepatic origin

THURSDAY, Jan. 26 (HealthDay News) -- Mutations in genes encoding isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are present in about a quarter of biliary tract carcinomas arising within the liver, according to a study published online Dec. 16 in The Oncologist.

Darrell R. Borger, Ph.D., from the Massachusetts General Hospital Cancer Center in Boston, and colleagues performed genotyping of 287 gastrointestinal tumors (biliary tract, colorectal, gastroesophageal, liver, pancreatic, and small intestine) for 130 known cancer-specific mutations within 15 cancer genes.

The researchers found that, while mutations in IDH1 were only present in 2 percent of all tumors, they were present in 25 percent of 12 biliary tract carcinomas. Further screening of an additional 75 gallbladder and bile duct cancers showed that mutations in IDH1 and IDH2 were present in 23 percent of cholangiocarcinomas of intrahepatic origin, but in none of the extrahepatic cholangiocarcinomas or gallbladder carcinomas. IDH1 mutation was associated with highly elevated levels of 2-hydroxyglutarate in an analysis of frozen tissue specimens.

"Thus, IDH1 mutation is a molecular feature of cholangiocarcinomas of intrahepatic origin. These findings define a specific metabolic abnormality in this largely incurable type of gastrointestinal cancer and present a potentially new target for therapy," the authors write.

Several authors disclosed financial ties to the pharmaceutical and biotechnology industries. Two authors hold intellectual property rights to the SNaPshot Genotyping Assay used in the study; one author is a co-inventor of discovery of neoactivity of IDH1 and IDH2 mutations.

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