1. Somatic Host Cell Alterations in HPV Carcinogenesis.
- Author
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Litwin TR, Clarke MA, Dean M, and Wentzensen N
- Subjects
- APOBEC Deaminases genetics, Class I Phosphatidylinositol 3-Kinases genetics, DNA Copy Number Variations, DNA, Viral genetics, Female, Genomic Instability, HLA Antigens genetics, Head and Neck Neoplasms genetics, Head and Neck Neoplasms virology, Humans, Mutation, Oncogene Proteins, Viral genetics, PTEN Phosphohydrolase genetics, Papillomaviridae genetics, Papillomavirus Infections genetics, Papillomavirus Infections virology, Receptor, Notch1 genetics, Tumor Suppressor Protein p53 genetics, Uterine Cervical Neoplasms genetics, Uterine Cervical Neoplasms virology, Carcinogenesis, Cell Transformation, Viral, Oncogene Proteins, Viral metabolism, Papillomavirus Infections complications
- Abstract
High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements. HPV-associated cancers have recurrent somatic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA ) and phosphatase and tensin homolog ( PTEN ), human leukocyte antigen A and B ( HLA-A and HLA-B ) -A/B , and the transforming growth factor beta (TGFβ) pathway, and rarely have mutations in the tumor protein p53 ( TP53 ) and RB transcriptional corepressor 1 ( RB1 ) tumor suppressor genes. There are some variations by tumor site, such as NOTCH1 mutations which are primarily found in head and neck cancers. Understanding the somatic events following HPV infection and persistence can aid the development of early detection biomarkers, particularly when mutations in precancers are characterized. Somatic mutations may also influence prognosis and treatment decisions., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
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