ASSOCIATION OF DNA METHYLATION OF P16INK4A CDKN2A AND MGMT GENES AND HISTOPATHOLOGICAL FEATURES OF BREAST CANCER

Abstract

Breast cancer(BC) is the most common tumorin women, and the second leading cause of death. Histopathology plays an important part in determining the treatment strategy for women with BC. DNA metylation is an important regulator of gene transcription.p16INK4a can block G1-S-phase progression and that mutant p16INK4a proteins are nonfunctional in cell cycle arrest or Cdk inhibition suggest that p16INK4a plays an important role in negative growth control. O6-methylguanine-DNA-methyltransferase(MGMT) is involved in direct cleavage of mutagenic alkyl adducts within DNA(direct DNA repair). In this study the promoter methylation levels of p16INK4a and MGMT genes which are associated with BC were investigated by Methylation-sensitive PCR. we analysed primary tumor core biopsies from 96 high-risk primary BC patients and their histopathologic types were associated with the methylation levels. In our study the promoter hypermethylation status were observed at different rates; p16INK4a and MGMT methlation frequencies were 43.8% and 34.4% respectively. The promoter hypermethylation levels of the genes found to be significant with ER positivity(+),PR(+),HER2/neu(+),e-cadherin(+) and Ki-67(<30%). In conclusion, our study shows that DNA methylation is a frequent event in BC and that different genes are methylated in BCs with different histopathological features.