Xueying Lyu, Karen Man-Fong Sze, Joyce Man-Fong Lee, Abdullah Husain, Lu Tian, Sandrine Imbeaud, Jessica Zucman-Rossi, Irene Oi-Lin Ng, Daniel Wai-Hung Ho
{"title":"肝细胞癌中病毒诱导结构变异的差异景观:机理特征和功能影响","authors":"Xueying Lyu, Karen Man-Fong Sze, Joyce Man-Fong Lee, Abdullah Husain, Lu Tian, Sandrine Imbeaud, Jessica Zucman-Rossi, Irene Oi-Lin Ng, Daniel Wai-Hung Ho","doi":"10.1097/hep.0000000000001087","DOIUrl":null,"url":null,"abstract":"Oncoviruses can integrate into the host genome and cause tumorigenesis. In particular, hepatitis B virus (HBV) infection accounts for more than 50% of hepatocellular carcinoma (HCC) worldwide. We revealed the global geographical disparity of HBV integration that the landscape of HBV integration between HCC tumor and non-tumorous liver varied in regional cohorts, suggesting the different degrees of clonal enrichment. Most HBV integrations were positionally enriched at telomeres and centromeres (T&C) and they highlighted the novel co-involvement of HBV integration, which likely introduces genomic instability in HCC development. This was confirmed by phospho-H2AX staining. We constructed a large meta-cohort of multiple ethnicities to refine the landscape of HBV integration. This enables the gene set/family level exploration. As <jats:italic toggle=\"yes\">TERT</jats:italic> is the most frequently integrated gene, we further investigated the underlying mechanistic modulation of <jats:italic toggle=\"yes\">TERT</jats:italic> transcription activation and revealed the concurrent influence by the orientation and relative distance of HBV integration. Additionally, clonal disparity of HBV integration was observed among patients and the higher level of clonal disparity score can indicate poor patients’ prognostication. Taken together, our study uncovered the different levels of clonal enrichment of HBV integration, mechanistic insights, and prognostic biomarker signature, to strengthen our understanding in HBV-associated hepatocarcinogenesis.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":null,"pages":null},"PeriodicalIF":12.9000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Disparity landscapes of viral-induced structural variations in hepatocellular carcinoma: Mechanistic characterization and functional implications\",\"authors\":\"Xueying Lyu, Karen Man-Fong Sze, Joyce Man-Fong Lee, Abdullah Husain, Lu Tian, Sandrine Imbeaud, Jessica Zucman-Rossi, Irene Oi-Lin Ng, Daniel Wai-Hung Ho\",\"doi\":\"10.1097/hep.0000000000001087\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Oncoviruses can integrate into the host genome and cause tumorigenesis. In particular, hepatitis B virus (HBV) infection accounts for more than 50% of hepatocellular carcinoma (HCC) worldwide. We revealed the global geographical disparity of HBV integration that the landscape of HBV integration between HCC tumor and non-tumorous liver varied in regional cohorts, suggesting the different degrees of clonal enrichment. Most HBV integrations were positionally enriched at telomeres and centromeres (T&C) and they highlighted the novel co-involvement of HBV integration, which likely introduces genomic instability in HCC development. This was confirmed by phospho-H2AX staining. We constructed a large meta-cohort of multiple ethnicities to refine the landscape of HBV integration. This enables the gene set/family level exploration. As <jats:italic toggle=\\\"yes\\\">TERT</jats:italic> is the most frequently integrated gene, we further investigated the underlying mechanistic modulation of <jats:italic toggle=\\\"yes\\\">TERT</jats:italic> transcription activation and revealed the concurrent influence by the orientation and relative distance of HBV integration. Additionally, clonal disparity of HBV integration was observed among patients and the higher level of clonal disparity score can indicate poor patients’ prognostication. 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Disparity landscapes of viral-induced structural variations in hepatocellular carcinoma: Mechanistic characterization and functional implications
Oncoviruses can integrate into the host genome and cause tumorigenesis. In particular, hepatitis B virus (HBV) infection accounts for more than 50% of hepatocellular carcinoma (HCC) worldwide. We revealed the global geographical disparity of HBV integration that the landscape of HBV integration between HCC tumor and non-tumorous liver varied in regional cohorts, suggesting the different degrees of clonal enrichment. Most HBV integrations were positionally enriched at telomeres and centromeres (T&C) and they highlighted the novel co-involvement of HBV integration, which likely introduces genomic instability in HCC development. This was confirmed by phospho-H2AX staining. We constructed a large meta-cohort of multiple ethnicities to refine the landscape of HBV integration. This enables the gene set/family level exploration. As TERT is the most frequently integrated gene, we further investigated the underlying mechanistic modulation of TERT transcription activation and revealed the concurrent influence by the orientation and relative distance of HBV integration. Additionally, clonal disparity of HBV integration was observed among patients and the higher level of clonal disparity score can indicate poor patients’ prognostication. Taken together, our study uncovered the different levels of clonal enrichment of HBV integration, mechanistic insights, and prognostic biomarker signature, to strengthen our understanding in HBV-associated hepatocarcinogenesis.
期刊介绍:
HEPATOLOGY is recognized as the leading publication in the field of liver disease. It features original, peer-reviewed articles covering various aspects of liver structure, function, and disease. The journal's distinguished Editorial Board carefully selects the best articles each month, focusing on topics including immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases, liver cancer, and drug metabolism.