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Promoter hypermethylation in primary squamous cell carcinoma of the oral cavity and oropharynx: a study of a Brazilian cohort

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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.

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Acknowledgments

We would like to thank PRPPG–UFES for donating methylSEQr™ Bisulfite Conversion Kits. MFCS was sponsored by a CAPES scholarship. We thank the Head and Neck Departments of the Araújo Jorge Hospital, GO and Santa Rita de Cássia Hospital, ES, Brazil for helping with sample collection.

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Authors and Affiliations

  1. 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

    Melissa de Freitas Cordeiro-Silva, Elaine Stur, Lidiane Pignaton Agostini & Iúri Drumond Louro

  2. Programa de Prevenção e Detecção Precoce do Câncer Bucal, Setor de Cirurgia de Cabeça e Pescoço Hospital Santa Rita de Cássia, Av. Marechal Campos, 1579. Santos Dumont, Vitoria, ES, CEP: 29040-091, Brazil

    José Roberto Vasconcelos de Podestá

  3. Divisão de Cirurgia de Cabeça e Pescoço, Hospital Araújo Jorge, Associação de Combate ao Câncer de Goiás, Rua 239, n. 181, St. Universitário, Goiânia, GO, 74605-070, Brazil

    José Carlos de Oliveira

  4. Faculdade de Odontologia, Universidade Federal de Goiás Campus 1, Sem Número, Praça Universitária, Goiânia, GO, 74605-020, Brazil

    Mariana Silveira Soares & Elismauro Francisco Mendonça

  5. Departamento de Ciências Fisiológicas Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468. Maruípe, Vitoria, ES, CEP: 29040-090, Brazil

    Sônia Alves Gouvea

  6. Departamento de Patologia Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468. Maruípe, Vitoria, ES, CEP: 29040-090, Brazil

    Sandra Ventorin Von Zeidler

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  1. Melissa de Freitas Cordeiro-Silva
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de Freitas Cordeiro-Silva, M., Stur, E., Agostini, L.P. et al. Promoter hypermethylation in primary squamous cell carcinoma of the oral cavity and oropharynx: a study of a Brazilian cohort. Mol Biol Rep 39, 10111–10119 (2012). https://doi.org/10.1007/s11033-012-1885-4

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