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Cell Lineage-Based Stratification for Glioblastoma.

ABSTRACT: Glioblastoma, the predominant adult malignant brain tumor, has been computationally classified into molecular subtypes whose functional relevance remains to be comprehensively established. Tumors from genetically engineered glioblastoma mouse models initiated by identical driver mutations in distinct cells of origin portray unique transcriptional profiles reflective of their respective lineage. Here, we identify corresponding transcriptional profiles in human glioblastoma and describe patient-derived xenografts with species-conserved subtype-discriminating functional properties. The oligodendrocyte lineage-associated glioblastoma subtype requires functional ERBB3 and harbors unique therapeutic sensitivities. These results highlight the importance of cell lineage in glioblastoma independent of driver mutations and provide a methodology for functional glioblastoma classification for future clinical investigations.

SUBMITTER: Wang Z

PROVIDER: S-EPMC7494533 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Cell Lineage-Based Stratification for Glioblastoma.

Wang Zilai Z Sun Daochun D Chen Yu-Jung YJ Xie Xuanhua X Shi Yufeng Y Tabar Viviane V Brennan Cameron W CW Bale Tejus A TA Jayewickreme Chenura D CD Laks Dan R DR Alcantara Llaguno Sheila S Parada Luis F LF

Cancer cell 20200709 3

Glioblastoma, the predominant adult malignant brain tumor, has been computationally classified into molecular subtypes whose functional relevance remains to be comprehensively established. Tumors from genetically engineered glioblastoma mouse models initiated by identical driver mutations in distinct cells of origin portray unique transcriptional profiles reflective of their respective lineage. Here, we identify corresponding transcriptional profiles in human glioblastoma and describe patient-de ...[more]

PMID: 32649888

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