Abstract 658: Methylation profile of CCNA1, MGMT, HIC1, TIMP3, AIM1, DAPK and CDH1 genes in head and neck cancer.

Abstract

Abstract Head and neck carcinomas are among the most frequent tumor types worldwide, with around 500,000 new cases diagnosed per year. The most common variant is the squamous cell carcinoma from the upper aerodigestive tract (HNSCC), representing 90% of these malignancies. Activation of proto-oncogenes and inactivation of tumor suppressor genes are the major genetic alterations involved in carcinogenesis. The increase in methylation in the promoter region of a tumor suppressor gene, or the lack of methylation of a proto-oncogene promoter region, can lead to progressive reduction/enhancement of its expression, resulting in its silencing, thus selecting cells with proliferative advantage. Promoter hypermethylation is considered a tumor marker in a variety of malignant neoplasias, including HNSCC. The objective of this work was to analyze the hypermethylation profile of CCNA1, MGMT, HIC1, TIMP3, AIM1, DAPK and CDH1 genes in DNA tumor samples of HNSCC patients included in Head and Neck Genome Project (GENCAPO). In this study, DNA was extracted from 33 tumor samples from HNSCC patients. Extracted DNA was submitted to bisulfite treatment and analyzed using Quantitative Methylation-Specific PCR (Q-MSP), this real-time PCR methodology allows a more objective, robust, and rapid assessment of promoter methylation status. Criteria for positive methylation of promoter regions by Q-MSP range from 0.01 to 100%. Our results showed that at least two of these genes were found methylated in 100% of the samples analyzed. In addition, the presence of promoter hypermethylation of Cyclin A1 (CCNA1) was significantly associated to absence of tobacco consumption (P=0.042). However, methylated DNA tumors were not associated with tumor site (CCNA1, P=0.55; MGMT, P=0.29; HIC1, P=1.00; TIMP3, P=1.00; AIM1, P=1.00 and DAPK, P=1.00) nor clinical stage (CCNA1, P=0.64; MGMT, P=0.38; HIC1, P=1.00; TIMP3, P=0.57; AIM1, P=0.55 and DAPK, P=1.00). In conclusion, the results suggest that hypermethylation of the CCNA1 gene is significantly associated to tobacco consumption in head and neck squamous cell carcinoma patients. Citation Format: Lidia Maria R B Arantes, Ana Carolina de Carvalho, Matias Eliseo Melendez, Eloiza Elena Tajara, Eny Maria Goloni-Bertollo, André L. Carvalho, Head and Neck Genome Project GENCAPO. Methylation profile of CCNA1, MGMT, HIC1, TIMP3, AIM1, DAPK and CDH1 genes in head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 658. doi:10.1158/1538-7445.AM2013-658