Detection of RASSF1A and RARβ hypermethylation in serum DNA from breast cancer patients

Shruti Shukla, Sameer Mirza, Gayatri Sharma, Rajinder Parshad, Siddhartha Datta Gupta, Ranju Ralhan

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Breast cancer is fast emerging as the leading cancer amongst females, especially in young females in metropolitan cities in India. The epigenetic alterations involved in the onset and progression of breast cancer may serve as biomarkers for early detection and prognosis of the disease. Furthermore, using body fluids such as serum offers a noninvasive method to procure multiple samples for such analyses. In this study, we examined methylation status of two normally unmethylated but biologically significant cancer genes, RAS association domain family protein 1A (RASSF1A) and retionic acid receptor β (RARβ) by methylation specific PCR (MSP) in invasive ductal carcinomas of the breast and paired serum DNA. RASSF1A was found to be methylated in 17 of 20 (85%) breast tumors; while sera from 15 of 20 (75%) of the patients showed concordant methylated RASSF1A, with a sensitivity of 88%. RARβ was methylated in 2/20 (10%) breast tumors. A gene unmethylated in the tumor DNA was always found to be unmethylated in the matched serum DNA for both RASSF1A and RARβ genes; hence specificity was 100%. Immunohistochemical analysis of RARβ protein in 15 breast carcinoma patients harboring unmethylated RARβ in tumors and serum DNA showed the expression of RARβ protein in tumors and paired normal breast tissues, confirming the MSP findings, suggesting that RARβ promoter is functional in these cases. This study underscores the potential utility of DNA methylation based screening of serum, a readily accessible body fluid, as a surrogate marker for early detection of breast cancer.

Original languageEnglish (US)
Pages (from-to)88-93
Number of pages6
JournalEpigenetics
Volume1
Issue number2
DOIs
StatePublished - 2006

Keywords

  • Breast Cancer
  • Methylation
  • RARβ
  • RASSF1A
  • Serum

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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