MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance.

ABSTRACT:

Purpose

Over the past few years, the alkylating agent temozolomide has become the standard-of-care therapy for patients with glioblastoma, the most common brain tumor. Recently, large-scale cancer genome sequencing efforts have identified a hypermutation phenotype and inactivating MSH6 mismatch repair gene mutations in recurrent, post-temozolomide glioblastomas, particularly those growing more rapidly during temozolomide treatment. This study aimed to clarify the timing and role of MSH6 mutations in mediating glioblastoma temozolomide resistance.

Experimental design

MSH6 sequence and microsatellite instability (MSI) status were determined in matched prechemotherapy and postchemotherapy glioblastomas identified by The Cancer Genome Atlas (TCGA) as having posttreatment MSH6 mu

SUBMITTER: Yip S 

PROVIDER: S-EPMC2737355 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature