Title

Relapse pathway of glioblastoma revealed by single-cell molecular analysis.

Document Type

Article

Publication Date

7-3-2018

Abstract

Glioblastoma multiforme (GBM) remains an incurable brain tumor. The highly malignant behavior of GBM may, in part, be attributed to its intraclonal genetic and phenotypic diversity (subclonal evolution). Identifying the molecular pathways driving GBM relapse may provide novel, actionable targets for personalized diagnosis, characterization of prognosis and improvement of precision therapy. We screened single-cell transcriptomes, namely RNA-seq data of primary and relapsed GBM tumors from a patient, to define the molecular profile of relapse. Characterization of hundreds of individual tumor cells identified three mutated genes within single cells, involved in the RAS/GEF GTP-dependent signaling pathway. The identified molecular pathway was further verified by meta-analysis of RNA-seq data from more than 3000 patients. This study showed that single-cell molecular analysis overcomes the inherent heterogeneity of bulk tumors with respect to defining tumor subclonal evolution relevant to GBM relapse.

Clinical Institute

Cancer

Clinical Institute

Neurosciences (Brain & Spine)

Department

Oncology

Department

Neurosciences

Volume

39

Issue

7

First Page

931

Last Page

936

PubMed ID

29718126

Journal Title

Carcinogenesis

Share

COinS