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Research Paper
Detection of RASSF1A and RAR? Hypermethylation in Serum DNA from Breast Cancer Patients
Shruti Shukla, Sameer Mirza, Gayatri Sharma, Rajinder Parshad, Siddhartha Datta Gupta and Ranju Ralhan
volume 1 | issue 2
april/may/june 2006Pages: 88 - 93
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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 non-invasive 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 ? (RAR?) 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%. RAR? 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 RAR? genes;
hence specificity was 100%. Immunohistochemical analysis of RAR? protein in 15 breast carcinoma
patients harboring unmethylated RAR? in tumors and serum DNA showed the expression of RAR?
protein in tumors and paired normal breast tissues, confirming the MSP findings, suggesting that
RAR? 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.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.