THE CORRELATİON BETWEEN LYMPH NODE METASTASİS AND METHYLATION IN BREAST CANCER

Abstract

Breast cancer (BC) is one of the most common malignancies with a high mortality rate among omen. Invasion and metastasis are two important hallmarks of malignant tumors associated with complex genetic and epigenetic alterations that allow tumors to disseminate throughout lymphatics of blood vessels, giving rise to the colonization and growth of metastatic cells in distant organs. considering that tumor dissemination is an earlyevent in BC, genetic and epigenetic analysis of tumors and metastatic lesions could provide results for biomarker discovery and may improve diagnosis, prognosis and proper management of the treatment for BC patients. the contribution of aberrant DNA hypermethylation of cancer related genes to the transcriptional silencing and carcinogenesis has been demonstrated in different diseases including different cancer types. we investigated the DNA methylation of MGMT, BMP6, p16INK4a, RINT1, THBS1 and TIMP3 genes by Methylation Sensitive PCR. DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched adjacent normal tissue from the same BC patients and the differences were significant for the p16INK4a and RINT1 promoterregions(p<0.05). MGMT and BMP6 (p<0.01), THBS1(p<0.001). Our results showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMp6, MGMT and THBS1 in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis.