Characterization of HPV and host genome interactions in primary head and neck cancers Journal Article


Authors: Parfenov, M.; Pedamallu, C. S.; Gehlenborg, N.; Freeman, S. S.; Danilova, L.; Bristow, C. A.; Lee, S.; Hadjipanayis, A. G.; Ivanova, E. V.; Wilkerson, M. D.; Protopopov, A.; Yang, L.; Seth, S.; Song, X.; Tang, J.; Ren, X.; Zhang, J.; Pantazi, A.; Santoso, N.; Xu, A. W.; Mahadeshwar, H.; Wheeler, D. A.; Haddad, R. I.; Jung, J.; Ojesina, A. I.; Issaeva, N.; Yarbrough, W. G.; Hayes, D. N.; Grandis, J. R.; El-Naggar, A. K.; Meyerson, M.; Park, P. J.; Chin, L.; Seidman, J. G.; Hammerman, P. S.; Kucherlapati, R.; the Cancer Genome Atlas Network
Contributors: Ciriello, G.; Ladanyi, M.; Lee, W.; Ramirez, R.; Sander, C.; Shen, R.; Sinha, R.; Weinhold, N.; Taylor, B. S.; Aksoy, B. A.; Dresdner, G.; Gao, J.; Gross, B.; Jacobsen, A.; Reva, B.; Schultz, N.; Sumer, S. O.; Sun, Y.; Chan, T.; Morris, L.
Article Title: Characterization of HPV and host genome interactions in primary head and neck cancers
Abstract: Previous studies have established that a subset of head and neck tumors contains human papillomavirus (HPV) sequences and that HPV-driven head and neck cancers display distinct biological and clinical features. HPV is known to drive cancer by the actions of the E6 and E7 oncoproteins, but the molecular architecture of HPV infection and its interaction with the host genome in head and neck cancers have not been comprehensively described. We profiled a cohort of 279 head and neck cancers with next generation RNA and DNA sequencing and show that 35 (12.5%) tumors displayed evidence of high-risk HPV types 16, 33, or 35. Twenty-five cases had integration of the viral genome into one or more locations in the human genome with statistical enrichment for genic regions. Integrations had a marked impact on the human genome and were associated with alterations in DNA copy number, mRNA transcript abundance and splicing, and both inter- and intrachromosomal rearrangements. Many of these events involved genes with documented roles in cancer. Cancers with integrated vs. nonintegrated HPV displayed different patterns of DNA methylation and both human and viral gene expressions. Together, these data provide insight into the mechanisms by which HPV interacts with the human genome beyond expression of viral oncoproteins and suggest that specific integration events are an integral component of viral oncogenesis.
Keywords: major clinical study; methylation; genetics; nonhuman; molecular genetics; dna methylation; physiology; virology; gene expression regulation; gene expression regulation, neoplastic; molecular sequence data; head and neck cancer; head and neck neoplasms; human genome; nucleotide sequence; base sequence; genome; dna sequence; gene dosage; tumor gene; virus genome; head and neck; head and neck tumor; genome, human; host pathogen interaction; rna transcription; rna sequence; wart virus; papilloma virus; genes, neoplasm; host-pathogen interactions; virus cell interaction; human papillomavirus type 16; papillomaviridae; virus dna cell dna interaction; virus integration; cancer; humans; human; article; integration sites; genome rearrangement; human papillomavirus type 33
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 111
Issue: 43
ISSN: 0027-8424
Publisher: National Academy of Sciences  
Date Published: 2014-10-28
Start Page: 15544
End Page: 15549
Language: English
DOI: 10.1073/pnas.1416074111
PUBMED: 25313082
PROVIDER: scopus
PMCID: PMC4217452
DOI/URL:
Notes: Article -- Export Date: 13 November 2017 -- Source: Scopus
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MSK Authors
  1. Timothy Chan
    222 Chan
  2. Ronglai Shen
    129 Shen
  3. Marc Ladanyi
    879 Ladanyi
  4. Luc Morris
    125 Morris
  5. Boris A Reva
    36 Reva
  6. Chris Sander
    196 Sander
  7. Rileen Sinha
    19 Sinha
  8. Jianjiong Gao
    63 Gao
  9. Barry Stephen Taylor
    144 Taylor
  10. Nikolaus D Schultz
    206 Schultz
  11. Benjamin E Gross
    26 Gross
  12. William Lee
    38 Lee
  13. Bulent Arman Aksoy
    33 Aksoy
  14. Selcuk Onur Sumer
    21 Sumer
  15. Yichao Sun
    12 Sun
  16. Ricardo   Ramirez
    19 Ramirez