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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