title: Correlation of somatic mutation and expression identifies genes important in human glioblastoma progression and survival.
abstract: Cooperative dysregulation of gene sequence and expression may contribute to cancer formation and progression. The Cancer Genome Atlas (TCGA) Network recently catalogued gene sequence and expression data for a collection of glioblastoma multiforme (GBM) tumors. We developed an automated, model-free method to rapidly and exhaustively examine the correlation among somatic mutation and gene expression and interrogated 149 GBM tumor samples from the TCGA. The method identified 41 genes whose mutation status is highly correlated with drastic changes in the expression (z-score ± 2.0), across tumor samples, of other genes. Some of the 41 genes have been previously implicated in GBM pathogenesis (e.g., NF1, TP53, RB1, and IDH1) and others, while implicated in cancer, had not previously been highlighted in studies using TCGA data (e.g., SYNE1, KLF6, FGFR4, and EPHB4). The method also predicted that known oncogenes and tumor suppressors participate in GBM via drastic over- and underexpression, respectively. In addition, the method identified a known synthetic lethal interaction between TP53 and PLK1, other potential synthetic lethal interactions with TP53, and correlations between IDH1 mutation status and the overexpression of known GBM survival genes.
authors.affiliation: Department of Biomedical Engineering and Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Masica
authors.forename: Rachel
authors.initials: R
authors.lastname: Karchin
mesh_terms: D000465:Algorithms; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis / Q000379:methods*; D018450:Disease Progression; D015870:Gene Expression; D053263:Gene Regulatory Networks; D016158:Genes, p53; D023281:Genomics / Q000379:methods*; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C415465:SYNE1 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human