Quantitative promoter hypermethylation profiles of ductal carcinoma in situ in North American and Korean women: Potential applications for diagnosis.

Abstract:

:To investigate the diagnostic potential of DNA methylation-based markers in tissue samples of DCIS, we examined the prevalence and extent of methylation in breast ductal carcinoma in situ (DCIS) samples from North American and Korean women. Quantitative multiplex-methylation specific PCR (QM-MSP) of ten genes was performed. The methylation level of APC1, Cyclin D2, HIN-1, RASSF1A and Twist singly, and cumulative methylation of all ten genes was significantly higher in DCIS compared to normal tissues for both groups. A three-gene panel (APC1, HIN-1 and RASSF1A) QM-MSP distinguished between DCIS and normal breast tissues with a sensitivity of 94 to 96% and a specificity of 81 to 87%. Methylation levels of these three genes in DCIS were higher than those of hyperplasia or adjacent normal appearing tissues in Korean women. Comparing North American and Korean DCIS, statistically significant differences in methylation levels were found for CDH1, ERalpha and RAR-beta. Quantification of gene methylation combined with immunohistochemistry in a small subset of tumors suggested that methylation may precede loss of protein expression for ERalpha. Our study demonstrated that methylation profiles of DCIS between North American and Korean women were similar. Methylation status of a panel of genes measured in a quantitative manner accurately discriminated between normal and DCIS tissues of both groups. For both North American and Korean women, QM-MSP analysis of a key panel of genes may be useful as an ancillary tool for DCIS detection in breast tissues.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Lee JS,Fackler MJ,Teo WW,Lee JH,Choi C,Park MH,Yoon JH,Zhang Z,Argani P,Sukumar S

doi

10.4161/cbt.7.9.6425

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

1398-406

issue

9

eissn

1538-4047

issn

1555-8576

pii

6425

journal_volume

7

pub_type

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