Genomic profiles of low-grade murine gliomas evolve during progression to glioblastoma.

ABSTRACT:

Background

Gliomas are diverse neoplasms with multiple molecular subtypes. How tumor-initiating mutations relate to molecular subtypes as these tumors evolve during malignant progression remains unclear.

Methods

We used genetically engineered mouse models, histopathology, genetic lineage tracing, expression profiling, and copy number analyses to examine how genomic tumor diversity evolves during the course of malignant progression from low- to high-grade disease.

Results

Knockout of all 3 retinoblastoma (Rb) family proteins was required to initiate low-grade tumors in adult mouse astrocytes. Mutations activating mitogen-activated protein kinase signaling, specifically KrasG12D, potentiated Rb-mediated tumorigenesis. Low-grade tumors showed mutant Kras-specific transcr

SUBMITTER: Vitucci M 

PROVIDER: S-EPMC5570221 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature