Abstract
Breast cancer susceptibility gene 1 (BRCA1), mapped on chromosome 17q21, is implicated in the mechanisms of cellular DNA repair. Inactivation of this gene is involved in the development of many human cancers, including breast cancer. This study aimed to investigate the prognostic value of BRCA1 promoter hypermethylation and expression in breast cancer cases. Sixty-one breast cancers were examined for BRCA1 hypermethylation by methylation-specific polymerase chain reaction (PCR), and 45 paired normal breast tissues were analyzed for altered BRCA1 mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction (qRT- PCR). Aberrant methylation status in BRCA1 was detected in 15 of 61 cases (24.6%), while reduced expression was found in 7 of 45 (15.6%). BRCA1 hypermethylation was statistically associated with tumor grade III (p=0.04), a high frequency of stage IIB (p=0.02), and triple-negative phenotype (OR= 3.64, 95%CI =1.1-12.3, p=0.03). Our findings indicated that BRCA1 promoter hypermethylation is a useful prognostic marker for breast cancer.
Highlights
Breast cancer susceptibility gene 1 (BRCA1) is mapped on chromosome 17q21; it encodes a multifunctional protein involved in DNA repair, cell-cycle check-point control, protein ubiquitinylation and chromatin remodeling (Miki et al, 1994; Ralhan et al, 2007)
Sixty-one breast cancers were examined for BRCA1 hypermethylation by methylation-specific polymerase chain reaction (PCR), and 45 paired normal breast tissues were analyzed for altered BRCA1 mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction
We evaluated BRCA1 promoter hypermethylation, since, gene expression might play a role in the development of breast cancer, and the correlation of BRCA1 hypermethylation and BRCA1
Summary
Breast cancer susceptibility gene 1 (BRCA1) is mapped on chromosome 17q21; it encodes a multifunctional protein involved in DNA repair, cell-cycle check-point control, protein ubiquitinylation and chromatin remodeling (Miki et al, 1994; Ralhan et al, 2007). Inactivation of this gene has been implicated in the development of many human cancers, including breast cancer. This study aimed to investigate the role of the BRCA1 hypermethylation epigenetic mechanism in Thai breast-cancer patients, to clarify the relevant prognostic biomarkers for breast cancer. We evaluated BRCA1 promoter hypermethylation, since, gene expression might play a role in the development of breast cancer, and the correlation of BRCA1 hypermethylation and BRCA1
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