Promoter hypermethylation of TMS1, BRCA1, ERα and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients

Sameer Mirza, Gayatri Sharma, Chandra P. Prasad, Rajinder Parshad, Anurag Srivastava, Siddartha Dutta Gupta, Ranju Ralhan

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)

Abstract

Breast cancer is fast emerging as the leading cancer amongst females, especially in younger age group in India; a large proportion of these tumors are often aggressive and ER and/or PR negative. Promoter methylation of genes involved in DNA repair and hormonal regulation may, in part, account for this behavior. To test this hypothesis methylation status of tumor suppressor genes TMS1, BRCA1, ERα and PRB was determined in invasive ductal carcinoma of breast and paired serum DNA. Of the 50 breast cancer patients investigated, 36/50 (72%) tumors and 32/50 (64%) paired sera showed methylation of at least one of these genes, while 17/50 (34%) tumors and 12/50 (24%) sera showed methylation of three genes. Methylation frequencies ranged from 24% for TMS1 to 63% for ERα. Significant association was observed between ERα and PRB methylation (p ≤ 0.001) and there was concordance between DNA methylation in tumor and serum for each gene. Immunohistochemical analysis showed no detectable expression of ERα, PRB and BRCA1 in 21/36 (58%), 20/36 (56%) and 23/36 (64%) tumors respectively; significant correlation was observed between promoter methylation and loss of protein expression confirming our hypothesis that promoter methylation is an important mechanism for transcriptional silencing of these genes in breast cancer in this population. This study also underscores the potential utility of DNA methylation based screening of serum (a surrogate for tumor DNA methylation) as a tool for detection of breast cancer.

Original languageEnglish
Pages (from-to)280-287
Number of pages8
JournalLife Sciences
Volume81
Issue number4
DOIs
Publication statusPublished - Jul 4 2007
Externally publishedYes

Keywords

  • BRCA1
  • ERα
  • Methylation
  • PRB
  • TMS1

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Pharmacology, Toxicology and Pharmaceutics

Fingerprint

Dive into the research topics of 'Promoter hypermethylation of TMS1, BRCA1, ERα and PRB in serum and tumor DNA of invasive ductal breast carcinoma patients'. Together they form a unique fingerprint.

Cite this