Biology of IDH mutant cholangiocarcinoma
Meng‐Ju Wu, Lei Shi, Joshua Merritt, Andrew X. Zhu, Nabeel Bardeesy – 27 February 2022 – Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are the most frequently mutated metabolic genes across human cancers. These hotspot gain‐of‐function mutations cause the IDH enzyme to aberrantly generate high levels of the oncometabolite, R‐2‐hydroxyglutarate, which competitively inhibits enzymes that regulate epigenetics, DNA repair, metabolism, and other processes. Among epithelial malignancies, IDH mutations are particularly common in intrahepatic cholangiocarcinoma (iCCA).