title: Integrated analysis of mutation data from various sources identifies key genes and signaling pathways in hepatocellular carcinoma.
abstract: BACKGROUND
  Recently, a number of studies have performed genome or exome sequencing of hepatocellular carcinoma (HCC) and identified hundreds or even thousands of mutations in protein-coding genes. However, these studies have only focused on a limited number of candidate genes, and many important mutation resources remain to be explored.
  
  
  RESULTS
  In this study, we integrated mutation data obtained from various sources and performed pathway and network analysis. We identified 113 pathways that were significantly mutated in HCC samples and found that the mutated genes included in these pathways contained high percentages of known cancer genes, and damaging genes and also demonstrated high conservation scores, indicating their important roles in liver tumorigenesis. Five classes of pathways that were mutated most frequently included (a) proliferation and apoptosis related pathways, (b) tumor microenvironment related pathways, (c) neural signaling related pathways, (d) metabolic related pathways, and (e) circadian related pathways. Network analysis further revealed that the mutated genes with the highest betweenness coefficients, such as the well-known cancer genes TP53, CTNNB1 and recently identified novel mutated genes GNAL and the ADCY family, may play key roles in these significantly mutated pathways. Finally, we highlight several key genes (e.g., RPS6KA3 and PCLO) and pathways (e.g., axon guidance) in which the mutations were associated with clinical features.
  
  
  CONCLUSIONS
  Our workflow illustrates the increased statistical power of integrating multiple studies of the same subject, which can provide biological insights that would otherwise be masked under individual sample sets. This type of bioinformatics approach is consistent with the necessity of making the best use of the ever increasing data provided in valuable databases, such as TCGA, to enhance the speed of deciphering human cancers.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yuannv
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ruqi
authors.initials: R
authors.lastname: Tang
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai, China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Lian
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xianghuo
authors.initials: X
authors.lastname: He
authors.affiliation: Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xie
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004252:DNA Mutational Analysis; D030561:Databases, Nucleic Acid; D066264:Datasets as Topic; D052138:Genes, Neoplasm; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics*