Computational and Systems Biology, Agency for Science Technology and Research, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore.
Graduate School of Integrative Sciences and Engineering, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 117456, Singapore.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.
Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Center Singapore, Singapore 169610, Singapore.
Duke-NUS Graduate Medical School Singapore, Singapore 169547, Singapore.
Hepatocellular carcinoma (HCC) is the cancer with the second highest mortality in the world due to its late presentation and limited treatment options. As such, there is an urgent need to identify novel biomarkers for early diagnosis and develop novel therapies. The availability of Next Generation Sequencing (NGS) data from tumors of liver cancer patients has provided us with invaluable resources to better understand HCC through the integration of data from different sources to facilitate the identification of promising biomarkers or therapeutic targets.
Here, we review key insights gleaned from over 20 NGS studies of HCC tumor samples, comprising approximately 582 whole genomes and 1211 whole exomes mainly from the East Asian population. Through consolidation of reported somatic mutations from multiple studies, we identified genes with different types of somatic mutations including single nucleotide variations, insertion/deletions, structural variations and copy number alterations as well as genes with multiple frequent viral integration. Pathway analysis showed that this curated list of somatic mutations is critically involved in cancer-related pathways, viral carcinogenesis and signalling pathways. Lastly, we addressed the future directions of HCC research as more NGS datasets become available.
Our review is a comprehensive resource for the current NGS research in HCC consolidating published articles, potential gene candidates and their related biological pathways.