Abstract 5177: Genome-wide profiling of somatic mutations in liver cancers revealed significantly mutated genes and non-coding regions in liver cancers

Abstract

Abstract Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Previously we have reported genomic aberrations detected by the whole genome sequencing (WGS) of 27 HCCs and frequently and recurrently mutated genes in this tumor (Nat Genet, 2012). Consistent with recent reports of WGS on human cancers from other groups, large parts of somatic point mutations (98.4%) were detected in non-coding genomic regions in our HCC samples. However, the consequence and significance of somatic mutations in non-coding regions are largely unknown. Here we analyzed 107 hepatitis C virus- (HCV-) associated HCCs by WGS analysis and calculated the somatic mutation rate of all single nucleotide variations (SNVs) and insertion-deletions (indels) within each 500-base bins on entire human genome. Among the whole genomic regions, 67 bins were significantly selected. After removing mutations in self-chained regions or simple repeat regions, which is expected to be false positives due to mapping errors, the bin containing exon 3 of CTNNB1 and multiple bins contains exons of TP53, which are known as driver mutations in HCCs, were highly ranked. In addition, entire coding region of the ALB gene showed high mutation rate compared with surrounding region distinctively. Interestingly, a recurrent short deletion on chromosome 18 was observed in the similar frequency as alterations of CTNNB1 or TP53. This short deletion was somatically detected in 35 of 321 liver cancers (10.9%) by Sanger sequencing. Significant accumulation of somatic mutations on exons of genes such as CTNNB1 and TP53 within entire genome through comparative analyses indicates their importance in hepatocarcinogenesis. Moreover, these results also suggest that novel mutations on non-coding regions, which are somatically and recurrently detected in higher rate in liver cancers, are involved in liver cancer development. These comprehensive approaches using WGS data will help the understanding of functions and alterations in non-coding regions occurred in cancer genome. Citation Format: Mayuko Furuta, Akihiro Fuimoto, Yuichi Shiraishi, Satoru Miyano, Tatsuhiko Tsunoda, Hidewaki Nakagawa. Genome-wide profiling of somatic mutations in liver cancers revealed significantly mutated genes and non-coding regions in liver cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5177. doi:10.1158/1538-7445.AM2014-5177