Abstract 577: Genetic and epigenetic alterations of the WWOX gene in head and neck cancer

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is a heterogenous disease and the 6th most frequent cancer in the world. Despite advances in medical treatment over the past two decades, the overall survival rate for patients with HNSCC remains around 50%. Well known environmental risk factors for developing HNSCC are cigarette smoking, especially in combination with alcohol consumption or tobacco chewing. In addition, many genetic and epigenetic changes are associated with sporadic HNSCC including alterations in the p53, VEGF and cyclin D1genes. Yet the molecular mechanisms of HNSCC carcinogenesis are still undergoing intensive investigation. The WWOX gene is located on a chromosomal fragile site 16q23.2 which spans the common fragile site FRA16D. It has been shown that exposure to environmental carcinogens such as smoking and alcohol consumption increases the potential for chromosomal breakage at the FRA16D site in esophageal and non-small cell lung cancers. On the other hand, genomic abnormalities affecting chromosome 16q are frequently reported in cytogenetic studies of various epithelial tumors, including prostate, breast, ovarian, esophageal, lung, gastric, and hepatocellular carcinomas. However, there is no data in the literature investigating the WWOX gene in the HNSCC. Therefore, the aim of this study was to determine the role of WWOX as a tumor suppressor gene in patients with HNSCC. For this purpose, tumor and corresponding normal tissue samples obtained from 75 patients with HNSCC were analyzed for mutations in the coding exons and the flanking intronic sequences by direct sequencing of the WWOX gene. mRNA expression levels were also analyzed by quantitative-real time-PCR and correlated with the methylation level of the WWOX gene promoter. The methylation status was determined by methylation-specific PCR(MSP). mRNA expression levels were significantly lower in tumor tissue than normal tissue (p≤0.001) and this downregulation was associated with hypermethylation of the promoter of the WWOX gene (p≤0.05). We identified 8 different alterations in the coding sequence of the WWOX gene with a frequency varying between 1.56-58.93%. Additionally, 17 different alterations in the noncoding regions were identified in our study group. Our results indicate that the WWOX gene may play an important role in the development of HNSCC. Citation Format: NUR BUYRU, Seda Ekizoglu, Hikmet Koseoglu, Emin Karaman. Genetic and epigenetic alterations of the WWOX gene in head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 577. doi:10.1158/1538-7445.AM2014-577