Targeting reduced mitochondrial DNA quantity as a therapeutic approach in pediatric high-grade gliomas.

ABSTRACT:

Background

Despite increased understanding of the genetic events underlying pediatric high-grade gliomas (pHGGs), therapeutic progress is static, with poor understanding of nongenomic drivers. We therefore investigated the role of alterations in mitochondrial function and developed an effective combination therapy against pHGGs.

Methods

Mitochondrial DNA (mtDNA) copy number was measured in a cohort of 60 pHGGs. The implication of mtDNA alteration in pHGG tumorigenesis was studied and followed by an efficacy investigation using patient-derived cultures and orthotopic xenografts.

Results

Average mtDNA content was significantly lower in tumors versus normal brains. Decreasing mtDNA copy number in normal human astrocytes led to a markedly increased tumorigenicity in vivo.

SUBMITTER: Shen H 

PROVIDER: S-EPMC6954438 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature