BRCA1 promoter methylation of normal breast epithelial cells as a possible precursor for BRCA1‐methylated breast cancer. Issue 10 (1st October 2014)

• Record Type: Journal Article
• Authors: Otani, Yoko; Miyake, Tomohiro; Kagara, Naofumi; Shimoda, Masafumi; Naoi, Yasuto; Maruyama, Naomi; Shimomura, Atsuhi; Shimazu, Kenzo; Kim, Seung Jin; Noguchi, Shinzaburo
• Is Part Of: Cancer science. Volume 105:Issue 10(2014:Oct.)
• Page Start: 1369
• Page End: 1376
• Publication Date: 2014-10-01
• Subjects: Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.12506
• Languages: English
• ISSNs: 1347-9032

Abstract

<abstract abstract-type="main" id="cas12506-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The breast cancer susceptibility gene 1 (<italic>BRCA1</italic>) and glutathione S‐transferase P1 (<italic>GSTP1</italic>) 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, <italic>BRCA1</italic> and <italic>GSTP1</italic> promoter methylation was examined by methylation‐specific PCR assay. Patients with <italic>BRCA</italic>1‐methylated (<italic>n</italic> = 15) or <italic>BRCA</italic>1‐unmethylated (<italic>n</italic> = 15) tumors and those with <italic>GSTP1</italic>‐methylated (<italic>n</italic> = 9) or <italic>GSTP1</italic>‐unmethylated (<italic>n</italic> = 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 (<italic>n</italic> = 1–5). Of the 15 patients with <italic>BRCA1</italic>‐methylated tumors, 9 harbored <italic>BRCA1</italic> promoter methylation in at least one site of the normal breast tissues. However, no <italic>BRCA1</italic> promoter methylation was observed at any site of the normal tissues of the 15 patients with <italic>BRCA1</italic>‐unmethylated tumors. No <italic>GSTP1</italic> promoter methylation was observed in the normal tissues regardless of the methylation status of the tumors. The presence of <italic>BRCA1</italic> 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 <italic>BRCA1</italic> promoter methylation can be precursor cells from which <italic>BRCA1</italic>‐methylated breast tumors may originate. This does not apply to <italic>GSTP1</italic> promoter methylation.</p> </abstract>