MGMT promoter methylation level in newly diagnosed low-grade glioma is a predictor of hypermutation at recurrence.

ABSTRACT:

Background

Emerging data suggest that a subset of patients with diffuse isocitrate dehydrogenase (IDH)-mutant low-grade glioma (LGG) who receive adjuvant temozolomide (TMZ) recur with hypermutation in association with malignant progression to higher-grade tumors. It is currently unclear why some TMZ-treated LGG patients recur with hypermutation while others do not. MGMT encodes O6-methylguanine-DNA methyltransferase, a DNA repair protein that removes cytotoxic and potentially mutagenic lesions induced by TMZ. Here, we hypothesize that epigenetic silencing of MGMT by promoter methylation facilitates TMZ-induced mutagenesis in LGG patients and contributes to development of hypermutation at recurrence.

Methods

We utilize a quantitative deep sequencing assay to characterize MGMT

SUBMITTER: Mathur R 

PROVIDER: S-EPMC8444710 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature