The somatic genomic landscape of glioblastoma

TCGA Research Network

Research output: Contribution to journalArticle

Abstract

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations areshown tocorrelate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

Original languageEnglish (US)
JournalCell
Volume155
Issue number2
DOIs
StatePublished - Oct 10 2013
Externally publishedYes

Fingerprint

Glioblastoma
Tumors
Telomerase
Biomarkers
Neoplasms
Genes
DNA Methylation
Survival Analysis
Proteomics
Messenger RNA
Phenotype
Mutation
Therapeutics
Research

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The somatic genomic landscape of glioblastoma. / TCGA Research Network.

In: Cell, Vol. 155, No. 2, 10.10.2013.

Research output: Contribution to journalArticle

TCGA Research Network. / The somatic genomic landscape of glioblastoma. In: Cell. 2013 ; Vol. 155, No. 2.
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abstract = "We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations areshown tocorrelate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.",
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