title: Promoter hypermethylation in primary squamous cell carcinoma of the oral cavity and oropharynx: a study of a Brazilian cohort.
abstract: Epigenetic silencing of cancer-related genes plays an important role in oral/oropharyngeal squamous cell carcinoma (OSCC). We evaluated promoter hypermethylation of 4 cancer-related genes in OSCCs of a Brazilian cohort and determined its relationship with exposure to alcohol, tobacco, HPV infection and clinicopathological parameters. CDKN2A (cyclin-dependent kinase inhibitor 2A or p16), SFN (stratifin or 14-3-3 σ), EDNRB (endothelin receptor B) and RUNX3 (runt-related transcript factor-3) had their methylation patterns evaluated by MSP analysis in OSCC tumors (n = 45). HPV detection was carried out by PCR/RFLP. Aberrant methylation was detected in 44/45 (97.8 %) OSCC; 24.4 % at CDKN2A, 77.8 % at EDNRB, 17.8 % at RUNX3 and 97.8 % at SFN gene. There was no significant association between methylation patterns and clinical parameters. HPV (subtype 16) was detected in 3 out of 45 patients (6 %). Our findings indicate that HPV infection is uncommon and methylation is frequent in Brazilian OSCCs, however, EDNRB and SFN gene methylation are not suitable OSCC biomarkers due to indistinct methylation in tumoral and normal samples. In contrast, CDKN2A and RUNX3 genes could be considered differentially methylated genes and potential tumor markers in OSCCs.
authors.affiliation: Núcleo de Genética Humana e Molecular Departamento de Ciências Biológicas, Centro de Ciências Humanas e Naturais Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468. Maruípe, Vitoria, ES, CEP: 29040-090, Brazil.
authors.forename: Melissa
authors.initials: M
authors.lastname: de Freitas Cordeiro-Silva
authors.forename: Elaine
authors.initials: E
authors.lastname: Stur
authors.forename: Lidiane Pignaton
authors.initials: LP
authors.lastname: Agostini
authors.forename: José Roberto Vasconcelos
authors.initials: JR
authors.lastname: de Podestá
authors.forename: José Carlos
authors.initials: JC
authors.lastname: de Oliveira
authors.forename: Mariana Silveira
authors.initials: MS
authors.lastname: Soares
authors.forename: Elismauro Francisco
authors.initials: EF
authors.lastname: Mendonça
authors.forename: Sônia Alves
authors.initials: SA
authors.lastname: Gouvea
authors.forename: Sandra Ventorin
authors.initials: SV
authors.lastname: Von Zeidler
authors.forename: Iúri Drumond
authors.initials: ID
authors.lastname: Louro
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000235:genetics; D001938:Brazil; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics* / Q000821:virology; D015331:Cohort Studies; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005092:Exonucleases / Q000235:genetics; D005095:Exoribonucleases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005814:Genes, Viral; D019942:Genes, p16; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology; D009959:Oropharyngeal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000821:virology; D030361:Papillomavirus Infections / Q000235:genetics* / Q000821:virology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D044023:Receptor, Endothelin B / Q000235:genetics; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000009:adverse effects
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D050677:Core Binding Factor Alpha 3 Subunit; D044023:Receptor, Endothelin B; C493729:Runx3 protein, human; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human