Divergent viral presentation among human tumors and adjacent normal tissues. Sci Rep 2016 Jun 24;6:28294
Date
06/25/2016Pubmed ID
27339696Pubmed Central ID
PMC4919655DOI
10.1038/srep28294Scopus ID
2-s2.0-84975700575 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets.
Author List
Cao S, Wendl MC, Wyczalkowski MA, Wylie K, Ye K, Jayasinghe R, Xie M, Wu S, Niu B, Grubb R 3rd, Johnson KJ, Gay H, Chen K, Rader JS, Dipersio JF, Chen F, Ding LAuthor
Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Central Nervous System NeoplasmsComputational Biology
Female
Gastrointestinal Neoplasms
Genetic Variation
Head and Neck Neoplasms
Hepatitis Viruses
Herpesviridae
Humans
Male
Neoplasms
Organ Specificity
Papillomaviridae
RNA, Viral
Sequence Analysis, RNA
Transcriptome
Virus Integration
Viruses
