Email this article Isocitrate dehydrogenase 1 and 2 genes mutations and MGMT methylation in gliomas
- Authors: Tabakov D.V.1, Katargin A.N.2, Stroganova A.M.1, Senderovich A.I.1, Naskhletashvili D.R.1, Kiseljova N.P.2
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Affiliations:
- Research Institute of Clinical Oncology, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
- Research Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
- Issue: Vol 4, No 1 (2017)
- Pages: 53-59
- Section: RESEARCH ARTICLES
- Published: 18.04.2017
- URL: https://umo.abvpress.ru/jour/article/view/89
- DOI: https://doi.org/10.17650/2313-805X-2017-4-1-53-59
- ID: 89
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Abstract
Gliomas are the most common brain tumors. It is difficult to detect them at early stages of disease and there is a few available therapies providing significant improvement in survival. Mutations of isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) play significant role in gliomogenesis, diagnostics and selection of patient therapy. We tested the distribution of IDH1 and IDH2 mutations in gliomas of different histological types and grades of malignancy by DNA melting analysis using our protocol with a sensitivity of 5 %. The results of this assay were confirmed by conventional Sanger sequencing. IDH1/2 mutations were detected in 74 % of lower grade gliomas (II and III, World Health Organization) and in 14 % of glioblastomas (IV, World Health Organization). Mutation rate in gliomas with oligodendroglioma component were significantly higher then in other glioma types (р = 0.014). The IDH1 mutations was the most common (79 % of general mutation number). IDH1/2 mutations can induce aberrant gene methylation. Detection of methylation rate of the gene encoding for O6-methylguanine-DNA-methyltransferase (MGMT), predictive biomarker for treatment of gliomas with the alkylating agents, has demonstrated a partial association with IDH1/2 mutations. In 73 % of IDH1/2-mutant tumors MGMT promoter methylation were observed. At the same time IDH1/2 mutations were not revealed in 67 % tumors with MGMT promoter methylation. These results indicate existence of another mechanism of MGMT methylation in gliomas. Our data strong support for necessity of both markers testing when patient therapy is selected.
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About the authors
D. V. Tabakov
Research Institute of Clinical Oncology, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Email: fake@neicon.ru
23 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
A. N. Katargin
Research Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Email: fake@neicon.ru
24 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
A. M. Stroganova
Research Institute of Clinical Oncology, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Email: fake@neicon.ru
23 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
A. I. Senderovich
Research Institute of Clinical Oncology, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Email: fake@neicon.ru
23 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
D. R. Naskhletashvili
Research Institute of Clinical Oncology, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Email: fake@neicon.ru
23 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
N. P. Kiseljova
Research Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center, Ministry of Health of Russia
Author for correspondence.
Email: natalia-kis@yandex.ru
24 Kashirskoye Shosse, Moscow 115478, Russia Russian Federation
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