Characterization of HPV and host genome interactions in primary head and neck cancers
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 molecu...
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| Format: | Article |
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National Academy of Sciences (U.S.)
2018
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| Online Access: | http://hdl.handle.net/1721.1/115484 |
| _version_ | 1826192788505493504 |
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| author | Freeman, Samuel Spenser Sharpe Jung, Joonil Ojesina, Akinyemi Meyerson, Matthew L. |
| author2 | Broad Institute of MIT and Harvard |
| author_facet | Broad Institute of MIT and Harvard Freeman, Samuel Spenser Sharpe Jung, Joonil Ojesina, Akinyemi Meyerson, Matthew L. |
| author_sort | Freeman, Samuel Spenser Sharpe |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:28:53Z |
| format | Article |
| id | mit-1721.1/115484 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:28:53Z |
| publishDate | 2018 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1154842022-09-30T14:42:43Z Characterization of HPV and host genome interactions in primary head and neck cancers Freeman, Samuel Spenser Sharpe Jung, Joonil Ojesina, Akinyemi Meyerson, Matthew L. Broad Institute of MIT and Harvard Massachusetts Institute of Technology. Department of Biology Freeman, Samuel Spenser Sharpe Jung, Joonil Ojesina, Akinyemi Meyerson, Matthew L 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. 2018-05-17T19:40:26Z 2018-05-17T19:40:26Z 2014-10 2018-05-07T15:10:08Z Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/115484 Parfenov, M. et al. “Characterization of HPV and Host Genome Interactions in Primary Head and Neck Cancers.” Proceedings of the National Academy of Sciences 111, 43 (October 2014): 15544–15549 http://dx.doi.org/10.1073/PNAS.1416074111 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Freeman, Samuel Spenser Sharpe Jung, Joonil Ojesina, Akinyemi Meyerson, Matthew L. Characterization of HPV and host genome interactions in primary head and neck cancers |
| title | Characterization of HPV and host genome interactions in primary head and neck cancers |
| title_full | Characterization of HPV and host genome interactions in primary head and neck cancers |
| title_fullStr | Characterization of HPV and host genome interactions in primary head and neck cancers |
| title_full_unstemmed | Characterization of HPV and host genome interactions in primary head and neck cancers |
| title_short | Characterization of HPV and host genome interactions in primary head and neck cancers |
| title_sort | characterization of hpv and host genome interactions in primary head and neck cancers |
| url | http://hdl.handle.net/1721.1/115484 |
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