The clinical value of aberrant epigenetic changes of DNA damage repair genes in human cancer

Abstract

The stability and integrity of the human genome are maintained by the DNA damage repair (DDR) system. Unrepaired DNA damage is a major source of potentially mutagenic lesions that drive carcinogenesis. In addition to gene mutation, DNA methylation occurs more frequently in DDR genes in human cancer. Thus, DNA methylation may play more important roles in DNA damage repair genes to drive carcinogenesis. Aberrant methylation patterns in DNA damage repair genes may serve as predictive, diagnostic, prognostic and chemosensitive markers of human cancer. MGMT methylation is a marker for poor prognosis in human glioma, while, MGMT methylation is a sensitive marker of glioma cells to alkylating agents. Aberrant epigenetic changes in DNA damage repair genes may serve as therapeutic targets. Treatment of MLH1-methylated colon cancer cell lines with the demethylating agent 5'-aza-2'-deoxycytidine induces the expression of MLH1 and sensitizes cancer cells to 5-fluorouracil. Synthetic lethality is a more exciting approach in patients with DDR defects. PARP inhibitors are the most effective anticancer reagents in BRCA-deficient cancer cells.

Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

“…In support of our findings, previous studies reported methylation of MGMT promoters in various types of cancers such as gastric cancer (36.8%), colorectal cancer (46%), lung cancer (21%), glioma (40%), head and neck cancers (60.8%), along with EC (44%). 38 Zhao et al 39 conducted a meta-analysis reporting the contribution of abnormal promoter methylation to the risk of EC. Whereas, contradictory findings also have been reported in Turkish population where MGMT promoter methylation showed no prognostic value in primary glioblastoma.…”

Base Excision Repair Manipulation in Breast Carcinoma: A Prospective Avenue to Potentiate Genome Insulting Approach

“…International Publisher [10][11][12][14][15][16]. There are growing thoughts that both normal and carcinoma cells instigate strategies to thwart such unfavorable genomic instability.…”

“…The DNA damage repair machinery of the both normal as well as breast carcinoma is responsible for maintenance of the genome integrity and stability along with needed manipulations during the state genomic insults imposed from outside [12,14,19]. The well-crafted DNA damage repair machinery inside the cell is tightly regulated and according the division of work inside the cellular periphery, a specific family of repair team agent is recruited when particular lesion is sensed.…”

“…BER is highlighted as the main process to maintain the integrity of the genome inflicted due to genotoxic agents [10][11][12]14]. The primary step in repairing a single base damage in DNA is glycosylase activities.…”

“…One of the plausible mechanisms behind above caveats is the role of abnormal and compensatory DNA repair among genotypically different breast carcinoma cells [8][9][10][11][12]. Chemotherapy and radiotherapy are widely opted mode of treatment for breast carcinoma but they do have setbacks [10,11,13,14].…”