Identification of Driver Genes in Hepatocellular Carcinoma by Exome Sequencing

Genetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma. As a prerequisite for individualized cancer treatment, we sought to characterize the landscape of recurrent somatic mutations in hepatocellular carcinoma. We performed whole exome sequencing on 87 hepatocellular carcinomas and matched normal adjacent tissues to an average coverage of 59x. The overall mutation rate was roughly 2 mutations per Mb, with a median of 45 non-synonymous mutations that altered the amino acid sequence (range 2 to 381). We found recurrent mutations in several genes with high transcript levels: TP53 (18%), CTNNB1 (10%), KEAP1 (8%), C16orf62 (8%), MLL4 (7%) and RAC2 (5%). Significantly affected gene families include the nucleotide-binding domain and leucine rich repeat containing family, calcium channel subunits, and histone methyltransferases. In particular, the... (for more see dbGaP study page.)

特定驱动基因的遗传改变会引发细胞通路紊乱，是肝细胞癌发生与进展的关键事件。作为癌症个体化治疗的前提，本研究旨在刻画肝细胞癌中复发性体细胞突变的全貌。我们对87例肝细胞癌及配对的癌旁正常组织开展全外显子组测序，平均测序深度达59倍。整体突变率约为每兆碱基2个突变，中位非同义突变数为45个（此类突变可改变氨基酸序列，突变数范围为2至381）。我们在多个高转录水平的基因中检测到复发性突变：TP53（18%）、CTNNB1（10%）、KEAP1（8%）、C16orf62（8%）、MLL4（7%）及RAC2（5%）。受显著影响的基因家族包括含核苷酸结合域与亮氨酸丰富重复序列的基因家族、钙离子通道亚基家族以及组蛋白甲基转移酶家族。具体而言，……（更多详情请参见dbGaP研究页面）