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...

Full description

Bibliographic Details
Main Authors: Pranav P. Mathkar, Xun Chen, Arvis Sulovari, Dawei Li
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/2/245
id doaj-8aefff20c93d4fd2af62f7ac73dfa937
record_format Article
spelling 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 AT pranavpmathkar characterizationofhepatitisbvirusintegrationsidentifiedinhepatocellularcarcinomagenomes
AT xunchen characterizationofhepatitisbvirusintegrationsidentifiedinhepatocellularcarcinomagenomes
AT arvissulovari characterizationofhepatitisbvirusintegrationsidentifiedinhepatocellularcarcinomagenomes
AT daweili characterizationofhepatitisbvirusintegrationsidentifiedinhepatocellularcarcinomagenomes
_version_ 1724284424872263680