Elucidation of
tumor-DNA virus associations in many
cancer types has enhanced our knowledge of fundamental
oncogenesis mechanisms and provided a basis for
cancer prevention initiatives.
RNA-Seq is a novel tool to comprehensively assess such associations. We interrogated
RNA-Seq data from 3,775
malignant neoplasms in The
Cancer Genome Atlas database for the presence of viral sequences. Viral integration sites were also detected in expressed transcripts using a novel approach. The detection capacity of
RNA-Seq was compared to available clinical laboratory data. Human papillomavirus (HPV) transcripts were detected using
RNA-Seq analysis in
head-and-neck squamous cell carcinoma, uterine
endometrioid carcinoma, and
squamous cell carcinoma of the lung. Detection of HPV by
RNA-Seq correlated with detection by in situ hybridization and immunohistochemistry in
squamous cell carcinoma tumors of the head and neck. Hepatitis B virus and Epstein-Barr virus (EBV) were detected using
RNA-Seq in
hepatocellular carcinoma and gastric
carcinoma tumors, respectively. Integration sites of viral genes and oncogenes were detected in
cancers harboring HPV or hepatitis B virus but not in EBV-positive gastric
carcinoma. Integration sites of expressed viral transcripts frequently involved known coding areas of the host genome. No DNA virus transcripts were detected in
acute myeloid leukemia, cutaneous
melanoma, low- and high-grade
gliomas of the brain, and
adenocarcinomas of the breast, colon and rectum, lung, prostate, ovary, kidney, and thyroid. In conclusion, this study provides a large-scale overview of the landscape of DNA viruses in human malignant
cancers. While further validation is necessary for specific
cancer types, our findings highlight the utility of
RNA-Seq in detecting
tumor-associated DNA viruses and identifying viral integration sites that may unravel novel mechanisms of
cancer pathogenesis.