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Review
, 7 (24), 37331-37346

The Clinical Value of Aberrant Epigenetic Changes of DNA Damage Repair Genes in Human Cancer

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Review

The Clinical Value of Aberrant Epigenetic Changes of DNA Damage Repair Genes in Human Cancer

Dan Gao et al. Oncotarget.

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.

Keywords: DNA damage repair; DNA methylation; MGMT; PARP inhibitor; synthetic lethality.

Conflict of interest statement

JGH is a consultant to MDxHealth. The other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. The application of abnormal epigenetic changes of DDR in human cancer

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