Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. Almost half of HCC cases are associated with hepatitis B virus (HBV) infections, which often lead to HBV sequence integrations in the human genome. Accurate identification of HBV integration sites at a single nucleotide r...
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doaj-8aefff20c93d4fd2af62f7ac73dfa9372021-02-05T00:06:33ZengMDPI AGViruses1999-49152021-02-011324524510.3390/v13020245Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma GenomesPranav P. Mathkar0Xun Chen1Arvis Sulovari2Dawei Li3Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USADepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USADepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USADepartment of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USAHepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. Almost half of HCC cases are associated with hepatitis B virus (HBV) infections, which often lead to HBV sequence integrations in the human genome. Accurate identification of HBV integration sites at a single nucleotide resolution is critical for developing a better understanding of the cancer genome landscape and of the disease itself. Here, we performed further analyses and characterization of HBV integrations identified by our recently reported VIcaller platform in recurrent or known HCC genes (such as <i>TERT</i>, <i>MLL4</i>, and<i> CCNE1</i>) as well as non-recurrent cancer-related genes (such as <i>CSMD2</i>,<i> NKD2</i>, and <i>RHOU</i>). Our pathway enrichment analysis revealed multiple pathways involving the alcohol dehydrogenase 4 gene, such as the metabolism pathways of retinol, tyrosine, and fatty acid. Further analysis of the HBV integration sites revealed distinct patterns involving the integration upper breakpoints, integrated genome lengths, and integration allele fractions between tumor and normal tissues. Our analysis also implies that the VIcaller method has diagnostic potential through discovering novel clonal integrations in cancer-related genes. In conclusion, although VIcaller is a hypothesis free virome-wide approach, it can still be applied to accurately identify genome-wide integration events of a specific candidate virus and their integration allele fractions.https://www.mdpi.com/1999-4915/13/2/245viral integrationvirome-wide detectionVIcallerintegration allele fractionhepatocellular carcinoma (HCC)hepatitis B virus (HBV) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pranav P. Mathkar Xun Chen Arvis Sulovari Dawei Li |
spellingShingle |
Pranav P. Mathkar Xun Chen Arvis Sulovari Dawei Li Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes Viruses viral integration virome-wide detection VIcaller integration allele fraction hepatocellular carcinoma (HCC) hepatitis B virus (HBV) |
author_facet |
Pranav P. Mathkar Xun Chen Arvis Sulovari Dawei Li |
author_sort |
Pranav P. Mathkar |
title |
Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes |
title_short |
Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes |
title_full |
Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes |
title_fullStr |
Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes |
title_full_unstemmed |
Characterization of Hepatitis B Virus Integrations Identified in Hepatocellular Carcinoma Genomes |
title_sort |
characterization of hepatitis b virus integrations identified in hepatocellular carcinoma genomes |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2021-02-01 |
description |
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. Almost half of HCC cases are associated with hepatitis B virus (HBV) infections, which often lead to HBV sequence integrations in the human genome. Accurate identification of HBV integration sites at a single nucleotide resolution is critical for developing a better understanding of the cancer genome landscape and of the disease itself. Here, we performed further analyses and characterization of HBV integrations identified by our recently reported VIcaller platform in recurrent or known HCC genes (such as <i>TERT</i>, <i>MLL4</i>, and<i> CCNE1</i>) as well as non-recurrent cancer-related genes (such as <i>CSMD2</i>,<i> NKD2</i>, and <i>RHOU</i>). Our pathway enrichment analysis revealed multiple pathways involving the alcohol dehydrogenase 4 gene, such as the metabolism pathways of retinol, tyrosine, and fatty acid. Further analysis of the HBV integration sites revealed distinct patterns involving the integration upper breakpoints, integrated genome lengths, and integration allele fractions between tumor and normal tissues. Our analysis also implies that the VIcaller method has diagnostic potential through discovering novel clonal integrations in cancer-related genes. In conclusion, although VIcaller is a hypothesis free virome-wide approach, it can still be applied to accurately identify genome-wide integration events of a specific candidate virus and their integration allele fractions. |
topic |
viral integration virome-wide detection VIcaller integration allele fraction hepatocellular carcinoma (HCC) hepatitis B virus (HBV) |
url |
https://www.mdpi.com/1999-4915/13/2/245 |
work_keys_str_mv |
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