@article{56fc46567a88418c9df1245aff93fd6a,
title = "Detection of RASSF1A and RARβ hypermethylation in serum DNA from breast cancer patients",
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.",
keywords = "Breast Cancer, Methylation, RARβ, RASSF1A, Serum",
author = "Shruti Shukla and Sameer Mirza and Gayatri Sharma and Rajinder Parshad and Gupta, {Siddhartha Datta} and Ranju Ralhan",
note = "Funding Information: Breast cancer is the third most common cancer in the world. Globally, it constitutes about 9% of all new cancers. Among women it ranks first comprising 18.4% of all cancers.1 (In India, breast cancer is the second most common cancer among females, while in the metropolitan cities of Delhi and Mumbai it ranks as the commonest cancer 2,3Till date mammography is the most prevalent screening strategy for breast cancer detection. However, sometimes it is associated with erroneous results and is often unable to detect breast cancer in early stages.4 Furthermore, mammography results often need to be corroborated with invasive and painful techniques such as trucut biopsies and fine needle aspirations, which require trained manpower and is often costly to the patient. Hence, the focus has increasingly We are grateful to Department of Biotechnology, shifted to identify novel screening/diagnostic strategies for risk assessment, early detection, India, for providing the financial support to conduct and monitoring prognosis of breast cancer. this study. S.M. is grateful to University Grant Breast cancer onset and progression is a multi step process resulting from a series of Commission for award of Junior Research Fellowship. epigenetic and genetic changes.5 Amongst the epigenetic mechanisms involved in the onset The authors thank Dr. Cecile Rochette Egly for the and progression of breast cancer is altered expression of multiple genes due to changes in kind gift of RARβ monoclonal antibody. the methylation status of CpG islands in their promoters and often coding regions too.6-9 Since aberrant gene methylation is one of the earliest molecular alterations occurring during cancer, it has emerged as a promising strategy for early detection of cancer.10-14 {\textcopyright} Recent studies suggest that methylation profiles of cancers are tumor type and ethnicity specific.15-17There are several reports on methylation profiles of breast cancer patients 2006 LADES BOSCECE from Western population.18-21 However, to our knowledge there is no study in the Indian population till date. Leon et al.22 demonstrated higher amounts of circulating DNA in the serum of patients with diverse metastatic neoplasms as compared to those with nonmetastatic tumors. Tumor-specific genetic or epigenetic alterations have been detected in serum DNA from renal, ovarian, gastric, head and neck, lung, and colon cancer patients.23-32 Importantly, these studies showed that tumor cell-specific DNA alterations in serum were not limited to patients with metastatic cancer, but could be detected in serum from patients with early or in situ cancer also. Neoplastic DNA in the serum most likely arises",
year = "2006",
doi = "10.4161/epi.1.2.2679",
language = "English (US)",
volume = "1",
pages = "88--93",
journal = "Epigenetics",
issn = "1559-2294",
publisher = "Taylor and Francis Ltd.",
number = "2",
}