title: Profiling of exome mutations associated with progression of HBV-related hepatocellular carcinoma.
abstract: Recent advances in sequencing technology have allowed us to profile genome-wide mutations of various cancer types, revealing huge heterogeneity of cancer genome variations. However, its heterogeneous landscape of somatic mutations according to liver cancer progression is not fully understood. Here, we profiled the mutations and gene expressions of early and advanced hepatocellular carcinoma (HCC) related with Hepatitis B-viral infection. Integrative analysis was performed with whole-exome sequencing and gene expression profiles of the 12 cases of early and advanced HCCs and paired non-tumoral adjacent liver tissues. A total of 293 tumor-specific somatic variants and 202 non-tumoral variants were identified. The tumor-specific variants were found to be enriched at chromosome 1q particularly in the advanced HCC, compared to the non-tumoral variants. Functional enrichment analysis revealed frequent mutations at the genes encoding cytoskeleton organization, cell adhesion, and cell cycle-related genes. In addition, to elucidate actionable somatic mutations, we performed an integrative analysis of gene mutations and gene expression profiles together. This revealed the 48 mutated genes which were differentially mutated with concomitant gene expression enrichment. Of these, CTNNB1 was found to have a pivotal role in the differential progression of the HCC subgroup. In conclusion, our integrative analysis of whole-exome sequencing and transcriptome profiles could provide actionable mutations which might play pivotal roles in the heterogeneous progression of HCC.
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea; Graduate School of Biomedical Science, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyun Goo
authors.initials: HG
authors.lastname: Woo
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Soon Sun
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea; Graduate School of Biomedical Science, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea; Graduate School of Biomedical Science, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: So Mee
authors.initials: SM
authors.lastname: Kwon
authors.affiliation: Graduate School of Biomedical Science, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Seun Joo
authors.initials: SJ
authors.lastname: Ahn
authors.affiliation: Institute for Medical Convergence, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Park
authors.affiliation: Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Cho
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cheong
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D060965:Clonal Evolution; D059472:Exome; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D051176:beta Catenin / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin