Shota Kawakami, Masaki Michishita, Motoharu Sakaue, Masami Morimatsu, Mitsuki Uemura, Nobuaki Kashiwagi, Marika Maeda, Yukino Machida, Daigo Azakami, Ai S Egusa, Eri Onozawa, Katsumi Ishioka, Masami Watanabe, Yoshikazu Tanaka, Toshinori Omi, Kazuhiko Ochiai
Isocitrate dehydrogenase 1 (IDH1) mutations are common in gliomas, acute myeloid leukemia, and chondrosarcoma. The mutation 'hotspot' is a single arginine residue, R132. The R132H mutant of IDH1 produces the 2-hydroxyglutarate (2-HG) carcinogen from α-ketoglutarate (α-KG). The reduction of α-KG induces the accumulation of hypoxia-inducible factor-1α subunit (HIF-1α) in the cytosol, which is a predisposing factor for carcinogenesis. R132H is the most common IDH1 mutation in humans, but mutations at the R132 residue can also occur in tumor tissues of dogs...
December 2020: Oncology Letters