Circulating Virus-Host Chimera DNAs in the Clinical Monitoring of Virus-Related Cancers

doi:10.3390/cancers14102531

Review

. 2022 May 20;14(10):2531.

doi: 10.3390/cancers14102531.

Circulating Virus-Host Chimera DNAs in the Clinical Monitoring of Virus-Related Cancers

Chiao-Ling Li¹, Shiou-Hwei Yeh^{1

2

3}, Pei-Jer Chen^{2

4

5}

Affiliations

¹ Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
² Center for Genomic Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
³ Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
⁴ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
⁵ Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.

PMID: 35626135
PMCID: PMC9139492
DOI: 10.3390/cancers14102531

Review

Circulating Virus-Host Chimera DNAs in the Clinical Monitoring of Virus-Related Cancers

Chiao-Ling Li et al. Cancers (Basel). 2022.

. 2022 May 20;14(10):2531.

doi: 10.3390/cancers14102531.

Authors

Chiao-Ling Li¹, Shiou-Hwei Yeh^{1

2

3}, Pei-Jer Chen^{2

4

5}

Affiliations

¹ Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
² Center for Genomic Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
³ Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
⁴ Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
⁵ Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.

PMID: 35626135
PMCID: PMC9139492
DOI: 10.3390/cancers14102531

Abstract

The idea of using tumor-specific cell-free DNA (ctDNA) as a tumor biomarker has been widely tested and validated in various types of human cancers and different clinical settings. ctDNA can reflect the presence or size of tumors in a real-time manner and can enable longitudinal monitoring with minimal invasiveness, allowing it to be applied in treatment response assessment and recurrence monitoring for cancer therapies. However, tumor detection by ctDNA remains a great challenge due to the difficulty in enriching ctDNA from a large amount of homologous non-tumor cell-free DNA (cfDNA). Only ctDNA with nonhuman sequences (or rearrangements) can be selected from the background of cfDNA from nontumor DNAs. This is possible for several virus-related cancers, such as hepatitis B virus (HBV)-related HCC or human papillomavirus (HPV)-related cervical or head and neck cancers, which frequently harbor randomly integrated viral DNA. The junction fragments of the integrations, namely virus-host chimera DNA (vh-DNA), can represent the signatures of individual tumors and are released into the blood. Such ctDNA can be enriched by capture with virus-specific probes and therefore exploited as a circulating biomarker to track virus-related cancers in clinical settings. Here, we review virus integrations in virus-related cancers to evaluate the feasibility of vh-DNA as a cell-free tumor marker and update studies on the development of detection and applications. vh-DNA may be a solution to the development of specific markers to manage virus-related cancers in the future.

Keywords: circulating tumor DNA (ctDNA); liquid biopsy; virus DNA integration; virus–host chimera DNA (vh-DNA).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Detection of somatic mutations and vh-DNA from cfDNA by targeted-NGS. Virus DNA integrates into the host genome during infection. Infected cells may undergo clonal expansion due to insertional mutagenesis and eventually become tumor cells through the accumulation of somatic mutations. As cell-free tumor markers, both tumor-specific somatic mutations and vh-DNA can be detected in plasma. However, the frequency of somatic mutations is low in cfDNA, while tumor-released vh-DNA is the main component of the total population of vh-DNA.

**Figure 2**
The potential applications of vh-DNA in tumor diagnosis and prognosis.

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[1] de Martel C., Georges D., Bray F., Ferlay J., Clifford G.M. Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis. Lancet Glob. Health. 2020;8:e180–e190. doi: 10.1016/S2214-109X(19)30488-7. - DOI - PubMed

[2] de Martel C., Georges D., Bray F., Ferlay J., Clifford G.M. Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis. Lancet Glob. Health. 2020;8:e180–e190. doi: 10.1016/S2214-109X(19)30488-7. - DOI - PubMed

[3] Plummer M., de Martel C., Vignat J., Ferlay J., Bray F., Franceschi S. Global burden of cancers attributable to infections in 2012: A synthetic analysis. Lancet Glob. Health. 2016;4:e609–e616. doi: 10.1016/S2214-109X(16)30143-7. - DOI - PubMed

[4] Plummer M., de Martel C., Vignat J., Ferlay J., Bray F., Franceschi S. Global burden of cancers attributable to infections in 2012: A synthetic analysis. Lancet Glob. Health. 2016;4:e609–e616. doi: 10.1016/S2214-109X(16)30143-7. - DOI - PubMed

[5] Ruan P., Dai X., Sun J., He C., Huang C., Zhou R., Cao Z., Ye L. Different types of viral-host junction found in HBV integration breakpoints in HBV-infected patients. Mol. Med. Rep. 2018;19:1410–1416. doi: 10.3892/mmr.2018.9709. - DOI - PMC - PubMed

[6] Ruan P., Dai X., Sun J., He C., Huang C., Zhou R., Cao Z., Ye L. Different types of viral-host junction found in HBV integration breakpoints in HBV-infected patients. Mol. Med. Rep. 2018;19:1410–1416. doi: 10.3892/mmr.2018.9709. - DOI - PMC - PubMed

[7] Ma N.-F., Lau S.H., Hu L., Xie D., Wu J., Yang J., Wang Y., Wu M.-C., Fung J., Bai X., et al. COOH-Terminal Truncated HBV X Protein Plays Key Role in Hepatocarcinogenesis. Clin. Cancer Res. 2008;14:5061–5068. doi: 10.1158/1078-0432.CCR-07-5082. - DOI - PubMed

[8] Ma N.-F., Lau S.H., Hu L., Xie D., Wu J., Yang J., Wang Y., Wu M.-C., Fung J., Bai X., et al. COOH-Terminal Truncated HBV X Protein Plays Key Role in Hepatocarcinogenesis. Clin. Cancer Res. 2008;14:5061–5068. doi: 10.1158/1078-0432.CCR-07-5082. - DOI - PubMed

[9] Decorsiere A., Mueller H., van Breugel P.C., Abdul F., Gerossier L., Beran R.K., Livingston C.M., Niu C., Fletcher S.P., Hantz O., et al. Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature. 2016;531:386–389. doi: 10.1038/nature17170. - DOI - PubMed

[10] Decorsiere A., Mueller H., van Breugel P.C., Abdul F., Gerossier L., Beran R.K., Livingston C.M., Niu C., Fletcher S.P., Hantz O., et al. Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor. Nature. 2016;531:386–389. doi: 10.1038/nature17170. - DOI - PubMed

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Circulating Virus-Host Chimera DNAs in the Clinical Monitoring of Virus-Related Cancers

Affiliations

Circulating Virus-Host Chimera DNAs in the Clinical Monitoring of Virus-Related Cancers

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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References

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