Correlation between CpG methylation profiles and hormone receptor status in breast cancers View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-08

AUTHORS

Weiwei Feng, Lanlan Shen, Sijin Wen, Daniel G Rosen, Jaroslav Jelinek, Xin Hu, Shaoyi Huan, Miao Huang, Jinsong Liu, Aysegul A Sahin, Kelly K Hunt, Robert C Bast, Yu Shen, Jean-Pierre J Issa, Yinhua Yu

ABSTRACT

INTRODUCTION: Aberrant DNA methylation has been found frequently in human breast cancers, associated with the loss of expression of a number of regulatory genes for growth and correlated to clinical outcomes. The present study was undertaken to determine whether methylation of a set of growth-suppressor genes would correlate to the expression of estrogen receptors (ERs) and progesterone receptors (PRs). METHODS: We used a pyrosequencing methylation analysis to study the methylation of 12 known growth-suppressor genes in 90 pairs of malignant/normal breast tissues. We also examined the expression of ERs and PRs in those specimens by immunohistochemistry. Mutations of p53 in tumor cells were detected by direct sequencing. RESULTS: Twelve tumor-suppressor genes: ARHI, RASSF1A, HIN-1, RARbeta2, hMLH1, 14-3-3 sigma, RIZ1, p16, E-cadherin, RIL, CDH13, and NKD2 were selected for this methylation study. Five of them (RIL, HIN-1, RASSF1A, CDH13, and RARbeta2) were frequently methylated in breast cancers (57%, 49%, 58%, 44%, and 17%, respectively) but not the normal breast (0-4%). Two panels of methylation profiles were defined. The methylation of the HIN-1/RASSFIA panel strongly correlated to the expression of ERs, PRs, and hormone receptors (HRs; which were defined as 'positive' if ERs and/or PRs were positive; p < 0.001). Conversely, the methylation of the RIL/CDH13 panel strongly correlated to negative ER, PR, and HR expression (p = 0.001, 0.025, and 0.001, respectively). The subset of triple-negative breast cancers (in other words, those with negative ER, PR, and HER-2/neu status) was positively associated with the methylation of the RIL/CDH13 panel and negatively associated with the HIN-1/RASSF1A panel. Mutations of p53 were found in nine breast tumors (11%), seven of which lacked methylation in both panels. CONCLUSION: We have defined two panels (HIN-1/RASSFIA, and RIL/CDH13) of methylation profiles, which correlated, either positively or negatively, to HR status. More... »

PAGES

r57

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/bcr1762

DOI

http://dx.doi.org/10.1186/bcr1762

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012833701

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17764565


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