Abstract 4902: Methylation profiles in head and neck cancer

Purpose: Among human malignancies, head and neck cancer (HNSCC) is the sixth most common cancer type in the world. Multiple genetic and epigenetic changes may contribute to the development of HNSCC. One of the epigenetic alterations, aberrant methylation in the promoter regions of multiple genes that lead to transcriptional silencing, has been shown in various cancer types including HNSCC. In this study we aimed to evaluate the epigenetic changes specific to HNSCC by investigating aberrant promoter hypermethylation of a panel of 24 tumor suppressor genes. Experimental Design: We investigated methylation of the promoter regions by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The methylation status of the selected genes were analyzed in 126 patients with HNSCC. Tumor and corresponding normal tissue samples were obtained during surgical resection. Probes added to the samples hybridized with their target sequence and were amplified by PCR depending on the methylation status of the target. The amplified products were detected by sequence type capillary electrophoresis. Peak sizes and areas were normalized and the relative signal peaks were compared to determine the methylation status. Results: 18 of 24 (75 %) genes displayed methylation in the tumor samples while none of the corresponding normal tissue samples were methylated. In 67.5 % (85/126) of the tumors the promoter regions were hypermethylated in at least one of the genes. The most frequently methylated genes were RARB (retinoic acid receptor beta), CHFR (checkpoint with forkhead and ring-finger domains) and CDH13 (Cadherin 13) genes. In 50 (39.7 %) patients, methylation was observed in more than one gene. Conclusions: Methylation of the CHFR, RARB and CDH13 gene promoters is a frequent event in HNSCC, demonstrating potential for these genes as biomarkers in detection strategies. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4902.