Promoter hypermethylation of p16INK4A, p14ARF, CyclinD2 and Slit2 in serum and tumor DNA from breast cancer patients

Gayatri Sharma, Sameer Mirza, Chandra P. Prasad, Anurag Srivastava, Siddhartha Dutta Gupta, Ranju Ralhan

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Epigenetic mechanisms such as DNA methylation play important role in cancer. Epigenetic alterations involved in the onset and progression of breast cancer may serve as biomarkers for early detection and prediction of disease prognosis. Furthermore, using body fluids such as serum offers a non-invasive method to procure multiple samples for biomarker analyses. The aim of this study is to determine the correlation between methylation status of multiple cancer genes, p16INK4A, p14ARF, Cyclin D2 and Slit2 in invasive ductal carcinoma of the breast and paired serum DNA and clinicopathological parameters. Of the 36 breast cancer patients investigated, 31 (86%) tumors and 30 (83%) paired sera showed methylation of at least one of these 4 genes. Methylation frequencies varied from 27% for CyclinD2, 44% for p16INK4A, 47% for p14ARF to 58% for Slit2. There was concordance between DNA methylation in tumor and paired serum DNA of each gene. This study underscores the potential utility of DNA methylation based screening of serum as a surrogate marker for tumor DNA methylation status of these genes in breast cancer. Further, expression profile of p16INK4A could be linked to epigenetic events, thus suggesting this pathway as a potential target for therapeutic strategies based on reversal of epigenetic silencing.

Original languageEnglish (US)
Pages (from-to)1873-1881
Number of pages9
JournalLife Sciences
Volume80
Issue number20
DOIs
StatePublished - Apr 24 2007
Externally publishedYes

Keywords

  • Breast cancer
  • Methylation
  • Serum

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • Pharmacology, Toxicology and Pharmaceutics(all)

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