Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell Carcinoma
Human Papilloma Virus (HPV) is highly prevalent within the U.S., with studies estimating that over 80% of individuals will contract the virus in their lifetime. HPV is considered a primary risk factor for the development and progression of oropharyngeal cancers. The impact of the HPV virus’s E6 and...
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/24/6190 |
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| author | Matthew Uzelac Armon Barakchi Varsha Beldona Daniel John Jaideep Chakladar Wei Tse Li Weg M. Ongkeko |
| author_facet | Matthew Uzelac Armon Barakchi Varsha Beldona Daniel John Jaideep Chakladar Wei Tse Li Weg M. Ongkeko |
| author_sort | Matthew Uzelac |
| collection | DOAJ |
| description | Human Papilloma Virus (HPV) is highly prevalent within the U.S., with studies estimating that over 80% of individuals will contract the virus in their lifetime. HPV is considered a primary risk factor for the development and progression of oropharyngeal cancers. The impact of the HPV virus’s E6 and E7 oncoproteins on cellular signaling pathways and genomic integration has been extensively characterized. Indirect genomic effects; however, remain relatively unidentified. In this study, we analyzed 83 HPV+ Head and Neck Squamous Cell Carcinoma (HNSCC) patients of varying HPV types. Expression counts of the HPV E6 and E7 oncogenes were estimated across samples and correlated with genomic mutational classes. High expression of E6 and E7 oncoproteins was associated with a greater number of total point mutations, especially on chromosomes 1, 11, and 17, which have been implicated in HPV-mediated cancers in previous studies. Samples with high E6 and E7 expression also exhibited more frequent non-clustered structural variation and a lack of clustered variation altogether. Copy number segments were present with fewer number of repeats in high E6 and E7 expression samples, which is known to correlate with decreased expression of affected genes. E6 and E7 expression was associated with increased activity of several cellular pathways associated in oncogenesis and telomere maintenance. In comprehensively characterizing the effects of the HPV oncoproteins on the human genome, potential mechanisms of HNSCC pathogenesis may be further elucidated. |
| first_indexed | 2024-03-09T17:14:23Z |
| format | Article |
| id | doaj.art-7377efcd7d944be58c264909aee371cc |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:14:23Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7377efcd7d944be58c264909aee371cc2023-11-24T13:47:44ZengMDPI AGCancers2072-66942022-12-011424619010.3390/cancers14246190Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell CarcinomaMatthew Uzelac0Armon Barakchi1Varsha Beldona2Daniel John3Jaideep Chakladar4Wei Tse Li5Weg M. Ongkeko6Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, CA 92093, USADivision of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, CA 92093, USADivision of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, CA 92093, USADivision of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, CA 92093, USADivision of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, CA 92093, USADivision of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, CA 92093, USADivision of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego, CA 92093, USAHuman Papilloma Virus (HPV) is highly prevalent within the U.S., with studies estimating that over 80% of individuals will contract the virus in their lifetime. HPV is considered a primary risk factor for the development and progression of oropharyngeal cancers. The impact of the HPV virus’s E6 and E7 oncoproteins on cellular signaling pathways and genomic integration has been extensively characterized. Indirect genomic effects; however, remain relatively unidentified. In this study, we analyzed 83 HPV+ Head and Neck Squamous Cell Carcinoma (HNSCC) patients of varying HPV types. Expression counts of the HPV E6 and E7 oncogenes were estimated across samples and correlated with genomic mutational classes. High expression of E6 and E7 oncoproteins was associated with a greater number of total point mutations, especially on chromosomes 1, 11, and 17, which have been implicated in HPV-mediated cancers in previous studies. Samples with high E6 and E7 expression also exhibited more frequent non-clustered structural variation and a lack of clustered variation altogether. Copy number segments were present with fewer number of repeats in high E6 and E7 expression samples, which is known to correlate with decreased expression of affected genes. E6 and E7 expression was associated with increased activity of several cellular pathways associated in oncogenesis and telomere maintenance. In comprehensively characterizing the effects of the HPV oncoproteins on the human genome, potential mechanisms of HNSCC pathogenesis may be further elucidated.https://www.mdpi.com/2072-6694/14/24/6190Human Papilloma Virus (HPV)Head and Neck Squamous Cell Carcinoma (HNSCC) |
| spellingShingle | Matthew Uzelac Armon Barakchi Varsha Beldona Daniel John Jaideep Chakladar Wei Tse Li Weg M. Ongkeko Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell Carcinoma Cancers Human Papilloma Virus (HPV) Head and Neck Squamous Cell Carcinoma (HNSCC) |
| title | Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell Carcinoma |
| title_full | Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell Carcinoma |
| title_fullStr | Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell Carcinoma |
| title_full_unstemmed | Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell Carcinoma |
| title_short | Effects of Human Papilloma Virus E6/E7 Oncoproteins on Genomic Structure in Head and Neck Squamous Cell Carcinoma |
| title_sort | effects of human papilloma virus e6 e7 oncoproteins on genomic structure in head and neck squamous cell carcinoma |
| topic | Human Papilloma Virus (HPV) Head and Neck Squamous Cell Carcinoma (HNSCC) |
| url | https://www.mdpi.com/2072-6694/14/24/6190 |
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