Open AccessBRCA 1 promoter methylation of normal breast epithelial cells as a possible precursor for BRCA 1 ‐methylated breast cancer
Author(s) -
Otani Yoko,
Miyake Tomohiro,
Kagara Naofumi,
Shimoda Masafumi,
Naoi Yasuto,
Maruyama Naomi,
Shimomura Atsuhi,
Shimazu Kenzo,
Kim Seung Jin,
Noguchi Shinzaburo
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12506
Subject(s) - methylation , gstp1 , carcinogenesis , cancer research , dna methylation , promoter , breast cancer , biology , microbiology and biotechnology , cancer , gene , gene expression , genetics , genotype
The breast cancer susceptibility gene 1 ( BRCA 1 ) and glutathione S‐transferase P1 ( GSTP 1 ) promoters are reportedly often methylated in breast cancer tissues. Their methylation status in surrounding normal breast tissues has not been examined thoroughly although this may well be important for a better understanding of breast carcinogenesis. In this study, BRCA 1 and GSTP 1 promoter methylation was examined by methylation‐specific PCR assay. Patients with BRCA 1‐methylated ( n = 15) or BRCA 1‐unmethylated ( n = 15) tumors and those with GSTP 1 ‐methylated ( n = 9) or GSTP 1 ‐unmethylated ( n = 11) tumors were included in the present study. Methylation status of manually micro‐dissected normal epithelial cells from the formalin‐fixed paraffin‐embedded sections of normal breast tissues adjacent to and distant from the tumors was examined at multiple sites ( n = 1–5). Of the 15 patients with BRCA 1 ‐methylated tumors, 9 harbored BRCA 1 promoter methylation in at least one site of the normal breast tissues. However, no BRCA 1 promoter methylation was observed at any site of the normal tissues of the 15 patients with BRCA 1 ‐unmethylated tumors. No GSTP 1 promoter methylation was observed in the normal tissues regardless of the methylation status of the tumors. The presence of BRCA 1 promoter methylation in the normal tissues was confirmed in the epithelial cells enriched with the magnetic‐activated cell sorting method. Our findings suggest that a small proportion of normal breast epithelial cells with BRCA 1 promoter methylation can be precursor cells from which BRCA 1 ‐methylated breast tumors may originate. This does not apply to GSTP 1 promoter methylation.