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Divergent viral presentation among human tumors and adjacent normal tissues
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Journal Article
Divergent viral presentation among human tumors and adjacent normal tissues
2016
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Central Nervous System Neoplasms - virology
/ Female
/ Gastrointestinal Neoplasms - virology
/ Genes
/ Genomes
/ Genomics
/ Head and Neck Neoplasms - virology
/ Hepatitis Viruses - genetics
/ Hepatitis Viruses - isolation & purification
/ Herpesviridae - isolation & purification
/ Humanities and Social Sciences
/ Humans
/ Male
/ Papillomaviridae - isolation & purification
/ RNA, Viral - isolation & purification
/ Science
/ Tumors
