Targetable signaling pathway mutations are associated with malignant phenotype in IDH-mutant gliomas.

ABSTRACT:

Purpose

Isocitrate dehydrogenase (IDH) gene mutations occur in low-grade and high-grade gliomas. We sought to identify the genetic basis of malignant phenotype heterogeneity in IDH-mutant gliomas.

Methods

We prospectively implanted tumor specimens from 20 consecutive IDH1-mutant glioma resections into mouse brains and genotyped all resection specimens using a CLIA-certified molecular panel. Gliomas with cancer driver mutations were tested for sensitivity to targeted inhibitors in vitro. Associations between genomic alterations and outcomes were analyzed in patients.

Results

By 10 months, 8 of 20 IDH1-mutant gliomas developed intracerebral xenografts. All xenografts maintained mutant IDH1 and high levels of 2-hydroxyglutarate on serial transplantation. All xenograft-pr

SUBMITTER: Wakimoto H 

PROVIDER: S-EPMC4070445 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature