RESUMEN

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.

Asunto(s)

Carcinoma de Células Escamosas/genética , Metilación de ADN , Neoplasias de la Boca/genética , Neoplasias Orofaríngeas/genética , Infecciones por Papillomavirus/genética , Regiones Promotoras Genéticas , Proteínas 14-3-3/genética , Adulto , Anciano , Anciano de 80 o más Años , Consumo de Bebidas Alcohólicas/efectos adversos , Biomarcadores de Tumor/genética , Brasil , Carcinoma de Células Escamosas/etiología , Carcinoma de Células Escamosas/virología , Estudios de Cohortes , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Epigénesis Genética , Exonucleasas/genética , Exorribonucleasas , Femenino , Regulación Neoplásica de la Expresión Génica , Genes Virales , Genes p16 , Papillomavirus Humano 16/genética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/etiología , Neoplasias de la Boca/virología , Neoplasias Orofaríngeas/etiología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Receptor de Endotelina B/genética , Factores de Riesgo , Análisis de Secuencia de ADN , Fumar/efectos adversos