The Somatic Genomic Landscape of Glioblastoma
Menée dans le cadre du projet "The Cancer Genome Atlas" portant sur plus de 500 échantillons tumoraux prélevés sur des patients atteints d'un glioblastome, cette étude décrit le paysage des altérations génomiques somatiques en association avec des caractéristiques cliniques
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 are shown to correlate 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. "Exome DNA sequencing in 291 glioblastomas, 42 with whole-genome sequencing"RNA sequencing of 164 glioblastomas identifies recurrent gene rearrangements "Copy-number, DNA methylation, protein, mRNA, and miRNA expression profiles of 543 GBMs "Integrated analysis of somatic alterations, molecular subtypes and affected pathways Integration of a large sample size of glioblastoma tumors with multidimensional omic characterization and clinical annotation provides new insights into driver mutations, distinctions between subtypes, and therapeutic options.