Investigation of BRCA1 methylation and FAT3 mutation as a potential biomarker in ovarian cancer samples

Ovarian cancer is one of the most dangerous and leading gynecological cancer with significant cancer related mortality among women. As the cancer detection is the key to increased survival, we aimed to test molecular markers in Ovarian Cancer (OC) Figo stage I, II and III tumor samples in order to identify genetic/epigenetic events having biomarker potential. Seven genes (BRCA1, IGFBP-3, DAPK1, RASSF1, CDKN2A, MLH1, and ANO5) were studied for their methylation status and three genes (FAT1, FAT3 and NF1) were tested for their mutation status on 24 ovarian cancer tumor samples and 10 normal ovarian tissue samples. The methylation frequency for BRCA1 and DAPK1 was found to be 83.3% and 8.3% respectively while no hypermethylation was observed for IGFBP-3, RASSF1, CDKN2A, ANO5 and MLH1 genes for selected CpG sites in all samples. BRCA1 hypermethylation was frequently found in serous (88.7%) than mucinous (66.6%) histotype (p < 0.035). Statistically, BRCA1 methylation was found commonly in older females (>45 year) (88%, n = 18), however, data was not significant (p < 0.25). BRCA1 methylation was also found to be associated with Figo stage III (78.5%) patients (p < 0.04), suggesting that this could be a late event in progression of ovarian cancers. Out of 24 OC samples, FAT1 (4.16%), FAT3(16.6%), and NF1 (8.3%) were found to be mutated for selected alleles. FAT3 mutation was recurrent in mucinous histology but did not display any significant correlation with clinic-pathological characteristics of tumor samples. Our study reports, frequent BRCA1 promoter methylation in serous and mucinous OC samples and therefore, it may serve as potential biomarker in therapeutic settings in future. FAT3 is an emerging diagnostic biomarker however, its clinical utility is required to be validated in a large cohort of ovarian cancer samples.