IDH1-R132H acts as a tumor suppressor in glioma via epigenetic up-regulation of the DNA damage response.

ABSTRACT: Patients with glioma whose tumors carry a mutation in isocitrate dehydrogenase 1 (IDH1^R132H) are younger at diagnosis and live longer. IDH1 mutations co-occur with other molecular lesions, such as 1p/19q codeletion, inactivating mutations in the tumor suppressor protein 53 (TP53) gene, and loss-of-function mutations in alpha thalassemia/mental retardation syndrome X-linked gene (ATRX). All adult low-grade gliomas (LGGs) harboring ATRX loss also express the IDH1^R132H mutation. The current molecular classification of LGGs is based, partly, on the distribution of these mutations. We developed a genetically engineered mouse model harboring IDH1^R132H, TP53 and ATRX inactivating mutations, and activated NRAS G12V. Previously, we

SUBMITTER: Nunez FJ 

PROVIDER: S-EPMC6400220 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature