Viral oncogenes, viruses, and cancer: a third-generation sequencing perspective on viral integration into the human genome

Abstract

The link between viruses and cancer has intrigued scientists for decades. Certain viruses have been shown to be vital in the development of various cancers by integrating viral DNA into the host genome and activating viral oncogenes. These viruses include the Human Papillomavirus (HPV), Hepatitis B and C Viruses (HBV and HCV), Epstein-Barr Virus (EBV), and Human T-Cell Leukemia Virus (HTLV-1), which are all linked to the development of a myriad of human cancers. Third-generation sequencing technologies have revolutionized our ability to study viral integration events at unprecedented resolution in recent years. They offer long sequencing capabilities along with the ability to map viral integration sites, assess host gene expression, and track clonal evolution in cancer cells. Recently, researchers have been exploring the application of Oxford Nanopore Technologies (ONT) nanopore sequencing and Pacific BioSciences (PacBio) single-molecule real-time (SMRT) sequencing in cancer research. As viral integration is crucial to the development of cancer via viruses, third-generation sequencing would provide a novel approach to studying the relationship interlinking viral oncogenes, viruses, and cancer. This review article explores the molecular mechanisms underlying viral oncogenesis, the role of viruses in cancer development, and the impact of third-generation sequencing on our understanding of viral integration into the human genome.

Tumor Antigens beyond the Human Exome

“…HPV16 is mostly responsible for 50% of cervical cancers and even higher rates at other sites of tumorigenesis [171]. In general, HPV carries the oncogenes E6, that degrades p53, and E7, that disrupts pRb, summarized in [172]. The expression of the other ORFs, E1, E2, E4, E5, L1, and L2, support the viral antigens E6 and E7 in oncogenesis [173,174].…”