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

Ji Shin Lee, Mary Jo Fackler, Wei Wen Teo, Jae Hyuk Lee, Chan Choi, Min Ho Park, Jung Han Yoon, Zhe Zhang, Pedram Argani, Saraswati Sukumar

Research output: Contribution to journalArticle

Abstract

To investigate the diagnostic potential of DNA methylationbased 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, ERα and RAR-β. Quantification of gene methylation combined with immunohistochemistry in a small subset of tumors suggested that methylation may precede loss of protein expression for ERα. 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.

Original languageEnglish (US)
Pages (from-to)1398-1406
Number of pages9
JournalCancer Biology and Therapy
Volume7
Issue number9
DOIs
StatePublished - Sep 2008

Fingerprint

Carcinoma, Intraductal, Noninfiltrating
Methylation
Genes
Polymerase Chain Reaction
Breast
Cyclin D2
Genetic Markers
Hyperplasia
Immunohistochemistry

Keywords

  • Breast cancer
  • Ductal carcinoma in situ
  • Geography
  • Methylation
  • Quantitation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology
  • Medicine(all)

Cite this

Quantitative promoter hypermethylation profiles of ductal carcinoma in situ in North American and Korean women : Potential applications for diagnosis. / Lee, Ji Shin; Fackler, Mary Jo; Teo, Wei Wen; Lee, Jae Hyuk; Choi, Chan; Park, Min Ho; Yoon, Jung Han; Zhang, Zhe; Argani, Pedram; Sukumar, Saraswati.

In: Cancer Biology and Therapy, Vol. 7, No. 9, 09.2008, p. 1398-1406.

Research output: Contribution to journalArticle

@article{e77f6d1770cc4fd383be4b5dbd99ff6d,
title = "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 methylationbased 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, ERα and RAR-β. Quantification of gene methylation combined with immunohistochemistry in a small subset of tumors suggested that methylation may precede loss of protein expression for ERα. 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.",
keywords = "Breast cancer, Ductal carcinoma in situ, Geography, Methylation, Quantitation",
author = "Lee, {Ji Shin} and Fackler, {Mary Jo} and Teo, {Wei Wen} and Lee, {Jae Hyuk} and Chan Choi and Park, {Min Ho} and Yoon, {Jung Han} and Zhe Zhang and Pedram Argani and Saraswati Sukumar",
year = "2008",
month = "9",
doi = "10.4161/cbt.7.9.6425",
language = "English (US)",
volume = "7",
pages = "1398--1406",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "9",

}

TY - JOUR

T1 - Quantitative promoter hypermethylation profiles of ductal carcinoma in situ in North American and Korean women

T2 - Potential applications for diagnosis

AU - Lee, Ji Shin

AU - Fackler, Mary Jo

AU - Teo, Wei Wen

AU - Lee, Jae Hyuk

AU - Choi, Chan

AU - Park, Min Ho

AU - Yoon, Jung Han

AU - Zhang, Zhe

AU - Argani, Pedram

AU - Sukumar, Saraswati

PY - 2008/9

Y1 - 2008/9

N2 - To investigate the diagnostic potential of DNA methylationbased 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, ERα and RAR-β. Quantification of gene methylation combined with immunohistochemistry in a small subset of tumors suggested that methylation may precede loss of protein expression for ERα. 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.

AB - To investigate the diagnostic potential of DNA methylationbased 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, ERα and RAR-β. Quantification of gene methylation combined with immunohistochemistry in a small subset of tumors suggested that methylation may precede loss of protein expression for ERα. 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.

KW - Breast cancer

KW - Ductal carcinoma in situ

KW - Geography

KW - Methylation

KW - Quantitation

UR - http://www.scopus.com/inward/record.url?scp=58149154845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58149154845&partnerID=8YFLogxK

U2 - 10.4161/cbt.7.9.6425

DO - 10.4161/cbt.7.9.6425

M3 - Article

C2 - 18769130

AN - SCOPUS:58149154845

VL - 7

SP - 1398

EP - 1406

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 9

ER -