Epigenetic modifications are essential regulators of biological processes. Decreased DNA methylation of OAS2 (2'-5'-Oligoadenylate Synthetase 2), encoding an antiviral protein, has been seen in psoriasis. To provide further insight into the epigenetic regulation of OAS2, we performed pyrosequencing to detect OAS2 DNA methylation status at 11 promoter and first exon located CpG sites in psoriasis (n = 12) and two common subtypes of squamous cell carcinoma (SCC) of the head and neck: tongue (n = 12) and tonsillar (n = 11). Compared to corresponding controls, a general hypomethylation was seen in psoriasis. In tongue and tonsillar SCC, hypomethylation was found at only two CpG sites, the same two sites that were least demethylated in psoriasis. Despite differences in the specific residues targeted for methylation/demethylation, OAS2 expression was upregulated in all conditions and correlations between methylation and expression were seen in psoriasis and tongue SCC. Distinctive methylation status at four successively located CpG sites within a genomic area of 63 bp reveals a delicately integrated epigenetic program and indicates that detailed analysis of individual CpGs provides additional information into the mechanisms of epigenetic regulation in specific disease states. Methylation analyses as clinical biomarkers need to be tailored according to disease-specific sites.

Department of Clinical Sciences ENT Umeå University Umeå Sweden

Department of Medical Biosciences Pathology Umeå University Umeå Sweden

Department of Public Health and Clinical Medicine Dermatology and Venereology Umeå University Umeå Sweden

Institut de Génétique Moléculaire Université Paris 7 Hôpital St Louis Paris France

RECAMO Masaryk Memorial Cancer Institute Brno Czech Republic

Zobrazit více v PubMed

Ziller M. J. PubMed PMC

Smith Z. D. & Meissner A. DNA methylation: roles in mammalian development. Nat. Rev. Genet. 14, 204–220 (2013). PubMed

Jones P. A. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat. Rev. Genet. 13, 484–492 (2012). PubMed

Plongthongkum N., Diep D. H. & Zhang K. Advances in the profiling of DNA modifications: cytosine methylation and beyond. Nat. Rev. Genet. 15, 647–661 (2014). PubMed

Schubeler D. Function and information content of DNA methylation. Nature 517, 321–326 (2015). PubMed

Bock C. Analysing and interpreting DNA methylation data. Nat. Rev. Genet. 13, 705–719 (2012). PubMed

Choi U. Y., Kang J. S., Hwang Y. S. & Kim Y. J. Oligoadenylate synthase-like (OASL) proteins: dual functions and associations with diseases. Exp. Mol. Med. 47, e144 (2015). PubMed PMC

Dar A. A. PubMed PMC

Mozzi A. PubMed PMC

Dan M., Zheng D., Field L. L. & Bonnevie-Nielsen V. Induction and activation of antiviral enzyme 2′,5′-oligoadenylate synthetase by PubMed

Dugan J. W. PubMed PMC

Perera G. K., Di Meglio P. & Nestle F. O. Psoriasis. Annu. rev. pathol. 7, 385–422 (2012). PubMed

Keermann M. PubMed PMC

Roberson E. D. PubMed PMC

Kamangar F., Dores G. M. & Anderson W. F. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J. Clin. Oncol. 24, 2137–2150 (2006). PubMed

Pezzuto F. PubMed

Gupta K. & Metgud R. Evidences suggesting involvement of viruses in oral squamous cell carcinoma. Pathol. Res. Int. 2013, 642496 (2013). PubMed PMC

Abogunrin S., Di Tanna G. L., Keeping S., Carroll S. & Iheanacho I. Prevalence of human papillomavirus in head and neck cancers in European populations: a meta-analysis. BMC Cancer 14, 968 (2014). PubMed PMC

Loizou C. PubMed PMC

Sgaramella N. PubMed PMC

Colella S., Shen L., Baggerly K. A., Issa J. P. & Krahe R. Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites. BioTechniques 35, 146–150 (2003). PubMed

Hoffmann M. PubMed

Detre S., Saclani Jotti G. & Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J. Clin. Pathol. 48, 876–878 (1995). PubMed PMC

Gu X., Nylander E., Coates P. J., Fahraeus R. & Nylander K. Correlation between Reversal of DNA Methylation and Clinical Symptoms in Psoriatic Epidermis Following Narrow-Band UVB Phototherapy. J. Invest. Dermatol. 135, 2077–2083 (2015). PubMed PMC

Gu X., Nylander E., Coates P. J. & Nylander K. Oxidation reduction is a key process for successful treatment of psoriasis by narrow-band UVB phototherapy. Acta Derm.-Venereol. 95, 140–146 (2015). PubMed

Roadmap Epigenomics C. PubMed PMC

Karolchik D. PubMed PMC

Lokk K. PubMed PMC

Bibikova M. PubMed

Peters T. J. PubMed PMC

Claus R. PubMed PMC

Nusgen N. PubMed PMC

Gutierrez-Arcelus M. Passive and active DNA methylation and the interplay with genetic variation in gene regulation. Life 2, e00523 (2013). PubMed PMC

Marchal C. & Miotto B. Emerging concept in DNA methylation: role of transcription factors in shaping DNA methylation patterns. J. Cell. Physiol. 230, 743–751 (2015). PubMed

Hovanessian A. G. & Justesen J. The human 2′-5′oligoadenylate synthetase family: unique interferon-inducible enzymes catalyzing 2′-5′ instead of 3′-5′ phosphodiester bond formation. Biochimie 89, 779–788 (2007). PubMed

Heyn H. & Esteller M. DNA methylation profiling in the clinic: applications and challenges. Nat. Rev. Genet. 13, 679–692 (2012). PubMed

Mikeska T. & Craig J. M. DNA methylation biomarkers: cancer and beyond. PubMed PMC

High immune cytolytic activity in tumor-free tongue tissue confers better prognosis in patients with squamous cell carcinoma of the oral tongue

AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck

Radiotherapy-Associated Long-term Modification of Expression of the Inflammatory Biomarker Genes ARG1, BCL2L1, and MYC