TY - JOUR T1 - Multi-modal meta-analysis of 1494 hepatocellular carcinoma samples reveals vast impacts of consensus driver genes on phenotypes JF - bioRxiv DO - 10.1101/166090 SP - 166090 AU - Kumardeep Chaudhary AU - Liangqun Lu AU - Olivier B Poirion AU - Sijia Huang AU - Travers Ching AU - Lana X Garmire Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/12/30/166090.abstract N2 - To characterize the phenotypic associations of driver genes in hepatocellular carcinoma (HCC), we identify 11 consensus driver genes across six HCC cohorts and 1,494 samples in total. The consensus driver genes include TP53, CTNNB1, ALB, AXIN1, RB1, ARID1A, RPS6KA3, ACVR2A, NFE2L2, CDKN2A and HNF1A. Integrative analysis of driver mutations, copy number variations and transcriptomic data reveals that these are associated with majority (63%) of the mRNA transcriptome, but only a small fraction (9%) of miRNAs. Genes associated with TP53, CTNNB1, ARID1A and HNF1A mutations contribute to four most densely connected clusters of biological pathways. Phenotypically, these driver genes are significantly associated with patients’ overall survival. Some driver genes are significantly linked to HCC gender and age disparities. CTNNB1, ALB and TP53 have higher relative risks (RR=1.2, 1.1 and 1.1) in males. Oppositely, AXIN1, which encodes axin-1, a component of the beta-catenin (encoded by CTNNB1) destruction complex has higher RR (1.6) in females. RB1 mutations are more frequent in younger patients (RR=1.3). This study consolidates a group of consensus driver genes in HCC, which collectively show vast impacts on the phenotypes. These driver genes may warrant as valuable therapeutic targets of HCC. ER -