Temporal and structural patterns of hepatitis B virus integrations in hepatocellular carcinoma. 2023

Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Chronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC). Notably, 90% of HBV-positive HCC cases exhibit detectable HBV integrations, hinting at the potential early entanglement of these viral integrations in tumorigenesis and their subsequent oncogenic implications. Nevertheless, the precise chronology of integration events during HCC tumorigenesis, alongside their sequential structural patterns, has remained elusive thus far. In this study, we applied whole-genome sequencing to multiple biopsies extracted from six HBV-positive HCC cases. Through this approach, we identified point mutations and viral integrations, offering a blueprint for the intricate tumor phylogeny of these samples. The emergent narrative paints a rich tapestry of diverse evolutionary trajectories characterizing the analyzed tumors. We uncovered oncogenic integration events in some samples that appear to happen before and during the initiation stage of tumor development based on their locations in reconstituted trajectories. Furthermore, we conducted additional long-read sequencing of selected samples and unveiled integration-bridged chromosome rearrangements and tandem repeats of the HBV sequence within integrations. In summary, this study revealed premalignant oncogenic and sequential complex integrations and highlighted the contributions of HBV integrations to HCC development and genome instability.

UI MeSH Term Description Entries
D008113 Liver Neoplasms Tumors or cancer of the LIVER. Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D002471 Cell Transformation, Neoplastic Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill. Neoplastic Transformation, Cell,Neoplastic Cell Transformation,Transformation, Neoplastic Cell,Tumorigenic Transformation,Cell Neoplastic Transformation,Cell Neoplastic Transformations,Cell Transformations, Neoplastic,Neoplastic Cell Transformations,Neoplastic Transformations, Cell,Transformation, Cell Neoplastic,Transformation, Tumorigenic,Transformations, Cell Neoplastic,Transformations, Neoplastic Cell,Transformations, Tumorigenic,Tumorigenic Transformations
D006509 Hepatitis B INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact. Hepatitis B Virus Infection
D006515 Hepatitis B virus The type species of the genus ORTHOHEPADNAVIRUS which causes human HEPATITIS B and is also apparently a causal agent in human HEPATOCELLULAR CARCINOMA. The Dane particle is an intact hepatitis virion, named after its discoverer. Non-infectious spherical and tubular particles are also seen in the serum. Dane Particle,Hepatitis Virus, Homologous Serum,B virus, Hepatitis,Hepatitis B viruses,Particle, Dane,viruses, Hepatitis B
D006528 Carcinoma, Hepatocellular A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested. Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D063646 Carcinogenesis The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years. Tumorigenesis,Oncogenesis,Carcinogeneses,Oncogeneses,Tumorigeneses

Related Publications

Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
February 2021, Viruses,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
March 1998, The Journal of general virology,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
March 2022, Gut,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
May 2005, Journal of hepatology,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
October 2008, World journal of gastroenterology,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
November 2001, Antiviral research,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
August 2010, Pathologie-biologie,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
November 1983, Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
January 2003, Journal of hepatology,
Haozhen Ren, and Xun Chen, and Jinglin Wang, and Ying Chen, and Alex Hafiz, and Qian Xiao, and Shiwei Fu, and Advaitha Madireddy, and Wei Vivian Li, and Xiaolei Shi, and Jian Cao
January 1996, Annals of the Academy of Medicine, Singapore,
Copied contents to your clipboard!