title: Co-mutated pathways analysis highlights the coordination mechanism in glioblastoma multiforme.
abstract: The mutation of cancer represents a high heterogeneity characteristic, setting a big obstacle in the mechanism study of it. In this study, we explored the distributions of mutated genes in pathways in glioblastoma multiforme (GBM), and constructed networks of co-mutated pathway pairs under the false discovery rate (FDR) control. By comparing the mutation frequencies, a total of 50 mutated genes were screened with the frequency > 3, and TP53, PTEN, and EGFR were the top 3 genes. By KEGG enrichment, 18 pathways of the mutation gene spectrum of GBM were enriched. These pathways were further studied to explore the coordination between pathways, co-mutated pathway pairs, such as mismatch repair/vascular smooth muscle contraction, mismatch repair/long-term depression, mismatch repair/dopaminergic synapse, and TGF-beta signaling pathway/retrograde endocannabinoid signaling pathway were enriched in the network under FDR < 0.01; and cell cycle/p53 signaling was a co-mutated pathway pairs in the network under FDR < 0.05. Meanwhile, the samples overlap levels of enriched pathways were calculated for further confirming of the co-mutated pathway model. By the co-mutated pathway analysis, the coordination mechanism of cancer can be explored, and it may provide basis for the pathogenesis and combined therapy study of cancer.
authors.forename: B
authors.initials: B
authors.lastname: Wei
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.forename: D
authors.initials: D
authors.lastname: Kong
authors.forename: G
authors.initials: G
authors.lastname: Hu
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
mesh_terms: D019295:Computational Biology / Q000379:methods*; D053263:Gene Regulatory Networks; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins