CpG hypomethylation of MDR1 gene in tumor and serum of invasive ductal breast carcinoma patients

Gayatri Sharma, Sameer Mirza, Rajinder Parshad, Anurag Srivastava, Siddartha Datta Gupta, Pranav Pandya, Ranju Ralhan

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Objectives: Multidrug resistance 1 (MDR1) gene encodes P-glycoprotein (P-gp), a transmembrane calcium-dependent efflux pump, implicated in drug resistance. In this prospective study, methylation status of MDR1 promoter and its correlation with clinicopathological parameters were evaluated in tumor and serum of breast cancer patients. Design and methods: Methylation-specific PCR was carried out to investigate the promoter methylation status of MDR1 in tumor and serum of 100 patients with invasive ductal carcinomas of breast (IDCs). The effect of promoter methylation on protein expression was evaluated by immunohistochemistry. Results: MDR1 was hypomethylated in 47% tumors and 44% paired sera of IDC patients and correlated significantly with increased tumor size and advanced tumor stage. Promoter hypomethylation of MDR1 in serum DNA showed 98% specificity and 50% sensitivity. Conclusions: Hypomethylation of MDR1 promoter in IDCs accounted for P-gp overexpression and aggressive biologic behavior in a subset of patients. Detection of these epigenetic changes in circulating DNA may not only enhance insight into the biological behavior of the primary tumor of an individual but may also provide valuable information regarding prognosis that can be readily monitored throughout the disease course.

Original languageEnglish (US)
Pages (from-to)373-379
Number of pages7
JournalClinical Biochemistry
Volume43
Issue number4-5
DOIs
StatePublished - Mar 2010

Keywords

  • Breast cancer
  • CpG Hypomethylation
  • Invasive ductal carcinoma
  • MDR1
  • Prognosis

ASJC Scopus subject areas

  • Clinical Biochemistry

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