The BRCA1 Promoter Hypermethylation in The Blood DNA of Stage I/II Non-BRCA1/BRCA2 Patients

Abstract

Background: BRCA1 promoter methylation has been reported for over a decade, and the majority of them were found in sporadic cases. The role in genetic predisposition is awaiting to be elucidated. Methods: Of the case without a germline BRCA1 or BRCA2 mutation, and with/without paired tumour tissue was available for analysis, blood leukocyte (n=192) and corresponding tumour (n=87) DNA were subjected to bisulfite DNA modification. Methylation specific PCR (MS-PCR) was used to detect the presence of hypermethylation in the promoter of BRCA1. Control group from normal individual without BRCA1 and BRCA2 mutation were also investigated in the similar way. Result: Among blood DNA from the breast cancer patients, 15.6% was BRCA1 promoter hypermethylated. Hypermethylation was also detected in 9.2% cases with paired tumour (n=87). It implied that 50% of the hypermethylation in blood DNA can be identified in the corresponding tumour. Conclusions: BRCA1 promoter hypermethylation can be a frequent event in the high-risk breast cancer patients. The methylation can either be a germline predisposition or from the tumour cells that leak into the bloodstream. This hypermethylation event can be exploited as early detection of breast cancer due to the fact that all of them are classified as stage I/II. Meanwhile, it is important to confirm the origin of the BRCA1 promoter methylation in the patients.