Preferential MGMT hypermethylation in SDH-deficient wild-type GIST.

ABSTRACT:

Aims

Wild-type gastrointestinal stromal tumours (wtGIST) are frequently caused by inherited pathogenic variants, or somatic alterations in the succinate dehydrogenase subunit genes (SDHx). Succinate dehydrogenase is a key enzyme in the citric acid cycle. SDH deficiency caused by SDHx inactivation leads to an accumulation of succinate, which inhibits DNA and histone demethylase enzymes, resulting in global hypermethylation. Epigenetic silencing of the DNA repair gene MGMT has proven utility as a positive predictor of the therapeutic efficacy of the alklyating drug temozolomide (TMZ) in tumours such as glioblastoma multiforme. The aim of this study was to examine MGMT promoter methylation status in a large cohort of GIST.

Methods

MGMT methylation analysis was per

SUBMITTER: Giger OT 

PROVIDER: S-EPMC10804026 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature