Aberrant promoter methylation of the RASSF1A and APC genes in epithelial ovarian carcinoma development

Abstract

Tumor suppressor gene (TSG) silencing through promoter hypermethylation plays an important role in cancer development. The aim of this study was to assess the extent of methylation of the RASSF1A and APC TSG promoters in ovarian epithelial adenomas, low malignant potential tumours and carcinomas in order to reveal a role for epigenetic TSG silencing in the development of these ovarian malignancies. The promoter methylation status of the RASSF1A and APC genes was assessed in 19 benign cystadenomas, 14 low malignant potential (LMP) tumours, and 86 carcinomas using methylation specific PCR (MSP). The methylation frequencies of the RASSF1A and APC gene promoters in benign cystadenomas were found to be 37% and 16%, respectively. The LMP tumours exhibited RASSF1A and APC gene promoter methylation frequencies of 50% and 28%, respectively, whereas the carcinomas exhibited methylation frequencies of 58% and 29%, respectively. Methylation of either the RASSF1A or the APC gene promoter was encountered in 58% of the invasive carcinomas. The observed aberrant methylation frequencies of the RASSF1A and APC gene promoters indicate that an accumulation of epigenetic events at these specific TSG promoters may be associated with the malignant transformation of benign cystadenomas and LMP tumours to carcinomas.