Association of aberrant DNA methylation with clinicopathological features in breast cancer

Abstract

Abstract. Aberrant DNA methylation is responsible for the epigenetic silencing of genes associated with tumourigenesis and progression of cancer. In this study, we assessed the methylation status of eight genes in 49 snap-frozen primary breast tumours. Epigenetic alterations of 8 genes were analysed with methylation-specific polymerase chain reaction (MS-PCR) (DCR1, DAPK1, RASSF1A and DCR2) or methylationsensitive high-resolution melting analysis (MS-HRM) (APC, MGMT, GSTP1 and PTEN). MS-HRM performance was validated by bisulfite pyrosequencing regarding the methylation levels of MGMT. Promoter methylation was observed in APC 54.34%, 40.4% DCR1, 37.5% DAPK1, 33.3% RASSF1A, 22.44% MGMT, 16.6% GSTP1, 6% PTEN and 0% DCR2 promoters, respectively. Interestingly, 37 out of 49 cases (75.5%) displayed aberrant promoter methylation in at least one gene. An association of MGMT promoter methylation with age and tumour grade was recorded. Moreover, a correlation with advanced T-category was elicited for GSTP1, RASSF1 and DAPK1 promoter methylation. Finally, concurrent methylation of several genes showed a marginal statistical relationship with N-category. We conclude that APC, DCR1, DAPK1 and RASSF1A promoter methylation represents a common event in breast cancer tumourigenesis. Our results suggest that GSTP1, RASSF1, DAPK1 and MGMT may be implicated in the acquisition of a more aggressive phenotype in breast cancer.

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

“…Several previous reports of the literature suggest that MGMT hypermethylation results in gene silencing and increased rate of mutations in normal colonic mucosa that might represent an initiating step in the development of mismatch repair-deficient CRC. [22][23][24][25] We also observed an age-related increase in MGMT methylation in CRC tissues in agreement with previous reports by Tserga et al 26 that showed a correlation between age and MGMT promoter methylation in breast cancer specimens, and Menigatti et al 21 that showed an age related increase of MGMT methylation in healthy colonic mucosa samples. CDKN2A was methylated in 29% of CRC samples and both RASSF1A and hMLH1 in 16.8% of them; by contrast, they resulted methylated only in a few healthy mucosa tissues.…”

Discussion of Pathogen and Potential Therapeutic Strategy for Triple Negative Breast Cancer Based on a Rare Case Study

“…MGMT methylation correlates with the loss of MGMT expression that leads cells transform to cancer cells. MGMT methylation had been found in 22% breast cancer patients [6]. In our case, no MGMT expression was detected in specimens from TNBC tumor, which suggests that DNA methylation may be involved in the specific gene profile of the rare phenotype of the patient.…”

“…Barekati et al [5] recently studied methylation signature of lymph node metastases of breast cancer and found the heterogeneity of DNA methylation between primary tumor and metastatic lesion. The [6] O-methylguanine-DNA methyltransferase (MGMT) is enzyme play important role in DNA repair. MGMT methylation correlates with the loss of MGMT expression that leads cells transform to cancer cells.…”

Association Between MGMT Promoter Methylation and Breast Cancer: a Meta-Analysis

“…Moreover, O6-methylguanine has the tendency to pair with thymine during replication [22] and trigger the conversion of G-to-A during base-pairing, causing mutations together with other factors. The MGMT protein restores guanine and inactivates itself during the process [4], providing to the cell a significant defence mechanism against tumourigenesis [23]. MGMT methylation has been reported to occur in one-third of all breast cancers, irrespective of the hormone receptors and Her-2 status [24].…”