IDH1 mutation makes gliomas more prone to treatment

May 8, 2019 0 By FM

Felipe J. Nunez et al demonstrated in a study that low grade gliomas found to be frequently associated with mutation in isocitrate dehydrogenase-1 (IDH1) genes may be effectively treated with a combination of radio and chemotherapy. The researchers discovered that the mutation in IDH1 can help maintain genomic stability in tumours by enhancing DNA repair while making them less sensitive to radiation. The mice used in the study were genetically engineered to grow brain cancer cells that have the disease-causing mutations in IDH1, along with commonly found co-occurring mutations in TP53 (tumour suppressor protein 53) and ATRX (alpha thalassemia/mental retardation syndrome X-linked gene). The mice were found to live longer compared to the control mice whose tumours were programmed to have normal IDH1 while still harbouring the mutations in TP53 and ATRX. The study found that the IDH1 mutation made glioma cells less aggressive and enhanced DNA repair through epigenetic up-regulation of the ataxia-telangiectasia–mutated (ATM) signaling pathway in the tumour. It was found that pharmacological inhibition of ATM restored the tumours’ radiosensitivity. The findings help explain the better survival of patients with gliomas possessing IDH1 mutation, despite being less sensitive to radiation. Scientists further evinced that the translation of these findings to patients could improve the therapeutic efficacy of radiotherapy and consequently survival in these patients.

Source: Science Translational Medicine 13 Feb 2019: Vol. 11, Issue 479, eaaq1427 DOI: http://stm.sciencemag.org/content/11/479/eaaq1427/tab-article-info