title: Divergent viral presentation among human tumors and adjacent normal tissues.
abstract: 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.
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Cao
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.|Department of Genetics, Washington University, St. Louis, Missouri 63108, USA.|Department of Mathematics, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wendl
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Wyczalkowski
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.|Department of Pediatrics, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Wylie
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.|Department of Genetics, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Ye
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.|Department of Medicine, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Reyka
authors.initials: R
authors.lastname: Jayasinghe
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.|Department of Medicine, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Mingchao
authors.initials: M
authors.lastname: Xie
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Beifang
authors.initials: B
authors.lastname: Niu
authors.affiliation: Department of Surgery, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Grubb
authors.affiliation: Brown School Master of Public Health Program, Washington University in St. Louis, St. Louis, MO 63130, USA.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Johnson
authors.affiliation: Siteman Cancer Center, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Hiram
authors.initials: H
authors.lastname: Gay
authors.affiliation: The University of Texas MD Anderson Cancer Center, Department of Bioinformatics and Computational Biology, Houston, Texas 77030, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Janet S
authors.initials: JS
authors.lastname: Rader
authors.affiliation: Department of Medicine, Washington University, St. Louis, Missouri 63108, USA.|Siteman Cancer Center, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Dipersio
authors.affiliation: Department of Medicine, Washington University, St. Louis, Missouri 63108, USA.|Siteman Cancer Center, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: McDonnell Genome Institute, Washington University, St. Louis, Missouri 63108, USA.|Department of Genetics, Washington University, St. Louis, Missouri 63108, USA.|Department of Medicine, Washington University, St. Louis, Missouri 63108, USA.|Siteman Cancer Center, Washington University, St. Louis, Missouri 63108, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
mesh_terms: D016543:Central Nervous System Neoplasms / Q000821:virology; D019295:Computational Biology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000821:virology; D014644:Genetic Variation; D006258:Head and Neck Neoplasms / Q000821:virology; D006518:Hepatitis Viruses / Q000235:genetics / Q000302:isolation & purification; D006564:Herpesviridae / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics / Q000821:virology*; D009928:Organ Specificity; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D017423:Sequence Analysis, RNA; D059467:Transcriptome; D016662:Virus Integration; D014780:Viruses / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D012367:RNA, Viral