Adult Lineage-Restricted CNS Progenitors Specify Distinct Glioblastoma Subtypes

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2015 Oct 14

PMID 26461091

Citations 121

Authors

Sheila R Alcantara Llaguno

Zilai Wang

Daochun Sun

Jian Chen

Jing Xu

Euiseok Kim

Kimmo J Hatanpaa

Jack M Raisanen

Dennis K Burns

Jane E Johnson

Luis F Parada

Affiliations

Soon will be listed here.

Abstract

A central question in glioblastoma multiforme (GBM) research is the identity of the tumor-initiating cell, and its contribution to the malignant phenotype and genomic state. We examine the potential of adult lineage-restricted progenitors to induce fully penetrant GBM using CNS progenitor-specific inducible Cre mice to mutate Nf1, Trp53, and Pten. We identify two phenotypically and molecularly distinct GBM subtypes governed by identical driver mutations. We demonstrate that the two subtypes arise from functionally independent pools of adult CNS progenitors. Despite histologic identity as GBM, these tumor types are separable based on the lineage of the tumor-initiating cell. These studies point to the cell of origin as a major determinant of GBM subtype diversity.

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