Detection of temozolomide-induced hypermutation and response to PD-1 checkpoint inhibitor in recurrent glioblastoma.

ABSTRACT:

Background

Despite aggressive upfront treatment in glioblastoma (GBM), recurrence remains inevitable for most patients. Accumulating evidence has identified hypermutation induced by temozolomide (TMZ) as an emerging subtype of recurrent GBM. However, its biological and therapeutic significance has yet to be described.

Methods

We combined GBM patient and derive GBM stem cells (GSCs) from tumors following TMZ to explore response of hypermutant and non-hypermutant emergent phenotypes and explore the immune relevance of hypermutant and non-hypermutant states in vivo.

Results

Hypermutation emerges as one of two possible mutational subtypes following TMZ treatment in vivo and demonstrates distinct phenotypic features compared to non-hypermutant recurrent GBM. Hypermutant tu

SUBMITTER: Daniel P 

PROVIDER: S-EPMC9252128 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature