AI Article Synopsis
- Previous studies show that a subset of head and neck cancers is linked to HPV, which has unique biological features and drives cancer through E6 and E7 oncoproteins.
- Researchers analyzed 279 head and neck tumors and found that 12.5% had high-risk HPV types, with 25 tumors showing integration of the viral genome into human genes.
- The integration of HPV significantly affected the host genome, leading to changes in DNA copy number, mRNA levels, and genetic rearrangements, suggesting that viral integration is crucial for HPV's role in cancer development.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4217452 | PMC |
| http://dx.doi.org/10.1073/pnas.1416074111 | DOI Listing |
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