Abstract LB-231: Decoding complex patterns of structural variations in hepatocellular carcinoma.

Abstract

Abstract Elucidating the molecular basis of Hepatocellular Carcinoma (HCC) is crucial to developing targeted diagnostics and therapies for this deadly disease. Somatically acquired structural variations (SVs) can lead to oncogenic gene fusions and gene expression deregulation in tumors. Although recent studies have delineated HCC genomic alterations including copy number variations, somatic mutations and HBV integrations, the landscape of SVs remains poorly characterized in HCC. We have predicted 4,314 SVs including large-scale insertions, deletions, inversions and translocations based on the whole-genome sequencing data for 88 primary HCC tumor/non-tumor tissues. We identified chromothripsis in 5 HCC genomes (5.7%) recurrently affecting chromosomal arms 1q and 8q. TP53 and RB1 alterations appear to cause increased levels of genomic arrangement and chromosomal instability. Albumin (ALB) was found to be the most significantly affected by SVs and harbor genomic alterations including deactivating mutations and deletions in 10.2% of cohort. Integrative analysis revealed a causal link between genomic rearrangements and copy number variations, such as focal amplifications of the CCND1/FGF19 loci, and distinctive patterns of copy number variation flanking SV breakpoints. Furthermore, we predicted 260 gene fusions which frequently result in aberrant over-expression of the 3′ genes in tumors. Citation Format: Julio Fernandez-Banet, Nikki P. Lee, Kin Tak Chan, Huan Gao, Xiao Liu, Wing Kin Sun, Winnie Tan, Sheung Tat Fan, Ronnie T. Poon, Shiyong Li, Keith Ching, Paul Rejto, Mao Mao, Zhengyan Kan. Decoding complex patterns of structural variations in hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-231. doi:10.1158/1538-7445.AM2013-LB-231