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Viruses 2017, 9(8), 206; doi:10.3390/v9080206

Somatic Host Cell Alterations in HPV Carcinogenesis

1
Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute, Rockville, MD 20850, USA
2
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA
3
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, MD 20850, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Karl Munger
Received: 11 July 2017 / Revised: 24 July 2017 / Accepted: 25 July 2017 / Published: 3 August 2017
(This article belongs to the Special Issue Expert Views on HPV Infection)
View Full-Text   |   Download PDF [2013 KB, uploaded 3 August 2017]   |  

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. View Full-Text
Keywords: HPV; somatic mutation; cervical cancer; APOBEC; significantly mutated gene; copy number variation; chromosomal instability; head and neck cancer; integration HPV; somatic mutation; cervical cancer; APOBEC; significantly mutated gene; copy number variation; chromosomal instability; head and neck cancer; integration
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Litwin, T.R.; Clarke, M.A.; Dean, M.; Wentzensen, N. Somatic Host Cell Alterations in HPV Carcinogenesis. Viruses 2017, 9, 206.

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