Abstract 4443: Investigation of the promoter methylation status of the FHIT (fragile histidine triad) gene in larynx cancer

Purpose: Development of carcinoma is associated with epigenetic modifications. Methylation of CpG islands in the promoter regions can participate in gene silencing and promote tumor aggressiveness. The Fragile histidine triad (FHIT) gene, localized on chromosome 3, is a tumor suppressor gene and the abnormal methylation of FHIT. The FHIT regulates the G2/M cell cycle check point and apoptotic pathwaysin various types of cancer. Inactivation of FHIT due to methylation has been shown in breast, cervical, gastric and colon carcinomas. In our study, we evaluated the FHIT gene promoter methylation in patients with larynx carcinoma (LC). Experimental Design: Methylation of FHIT was investigated by bisulfite modification/methylation-specific polymerase chain reaction in tumors and matched normal tissue samples from 57 Turkish patients with LC. Results: The promoter region of the FHIT was methylated in 96.49% and 29.82% of the primary tumors and the corresponding normal tissue samples, respectively [p = 0.0001, chi-square = 14.2105, OR(95%CI) = 64.7(14.4-296.07)]. A methylation rate (less than 10%) was observed in 3.51% (2/57) and 70.18% (40/57) of tumor and normal samples, respectively. Moderate methylation levels (10-25%) were found in 3.51% (2/57) of the tumors and 1.75% (1/57) of the adjacent normal tissues. High methylation levels (>25%) were observed in 92.98% (53/57) and 28.07% (16/57) in the tumor and normal tissues, respectively. Conclusion: Methylation may play an important role in LC carcinogenesis. Although we found that there was significant association between the methylation levels of tumor and adjacent normal tissues, high methylation levels of the FHIT was observed in the tumors when compared to the levels in normal tissue. These results suggest that the methylation rates of FHIT gene may provide a suitable biomarker in LC carcinogenesis. Our study is still in progress to include a larger cohort of patients. Citation Format: Semra Demokan, Kubra Akalin, Cansu Ozkoklesen, Murat Ulusan, Necati Enver, Nejat Dalay. Investigation of the promoter methylation status of the FHIT (fragile histidine triad) gene in larynx cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4443.