Methylation status of HPV16 E2-binding sites classifies subtypes of HPV-associated oropharyngeal cancers

Cancer
M ReuschenbachMagnus von Knebel Doeberitz

Abstract

The human papillomavirus (HPV) E2 protein is a transcriptional repressor of the oncogenes E6/E7 and loss of E2 function is considered a key step in carcinogenesis. Integration of HPV into the host genome may disrupt the E2 gene. Furthermore, methylation of CpG dinucleotides in E2-binding sites (E2BSs) in the HPV upstream regulatory region may interfere with transcriptional repression of E6 and E7 by E2. The authors hypothesized that the CpG methylation status of E2BS identifies subtypes of HPV type 16 (HPV16)-associated oropharyngeal squamous cell cancers (OPSCC) in association with E2 gene integrity and viral integration. Methylation of 10 CpG dinucleotides within the upstream regulatory region, encompassing E2BSs 1, 2, 3, and 4, was quantitatively analyzed by bisulfite pyrosequencing in 57 HPV16-associated OPSCC cases. E2 status was analyzed by gene amplification and quantitative real-time reverse transcriptase-polymerase chain reaction. Viral integration was determined by integration-specific polymerase chain reaction methods. Three subgroups with differential methylation at E2BS3 and E2BS 4 were identified: 1) complete methylation (>80%) associated with the presence of integrated HPV genomes with an intact E2 gene; 2) inter...Continue Reading

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Citations

Dec 3, 2015·European Journal of Medical Genetics·Franziska AuerJulia Hauer
Jul 13, 2017·Viruses·Rachel Katzenellenbogen
Jan 31, 2020·International Journal of Cancer. Journal International Du Cancer·Takuya NakagawaAtsushi Kaneda
Jan 11, 2020·Seminars in Immunopathology·Megan BurleyJoanna L Parish
Jun 4, 2020·Cells·Chameera Ekanayake WeeramangeChamindie Punyadeera
Feb 13, 2018·Oncology Letters·Francisco Israel Torres-RojasBerenice Illades-Aguiar
Apr 7, 2017·PLoS Pathogens·Alison A McBride, Alix Warburton
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Aug 13, 2020·Cancers·Francisco AguayoDaniela Nuñez-Acurio
Dec 5, 2020·Molecular Cancer Therapeutics·Muriel Charlotte BernhardStefan Lohse
Dec 22, 2020·Frontiers in Cellular and Infection Microbiology·Nikita AggarwalAlok C Bharti
May 1, 2021·Microorganisms·Takuya NakagawaAtsushi Kaneda

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