TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo.

ABSTRACT:

Background

Heterozygous TERT (telomerase reverse transcriptase) promoter mutations (TPMs) facilitate TERT expression and are the most frequent mutation in glioblastoma (GBM). A recent analysis revealed this mutation is one of the earliest events in gliomagenesis. However, no appropriate human models have been engineered to study the role of this mutation in the initiation of these tumors.

Method

We established GBM models by introducing the heterozygous TPM in human induced pluripotent stem cells (hiPSCs) using a two-step targeting approach in the context of GBM genetic alterations, CDKN2A/B and PTEN deletion, and EGFRvIII overexpression. The impact of the mutation was evaluated through the in vivo passage and in vitro experiment and analysis.

Results

Orthotopic inject

SUBMITTER: Miki S 

PROVIDER: S-EPMC9713509 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature