Correlation of somatic mutation and expression identifies genes important in human glioblastoma progression and survival.
Correlation of somatic mutation and expression identifies genes important in human glioblastoma progression and survival.
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DOI：
10.1158/0008-5472.can-11-0180
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发表时间：
2011-07-01
期刊：
影响因子：
11.2
通讯作者：
Karchin R
中科院分区：
文献类型：
--
作者：
Masica DL;Karchin R
Cooperative dysregulation of gene sequence and expression may contribute to cancer formation and progression. The Cancer Genome Atlas (TCGA) Network recently cataloged 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 under-expression, respectively. Additionally, 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.
