Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 7 (24), 37331-37346

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


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

Dan Gao et al. Oncotarget.


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.


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

Similar articles

See all similar articles

Cited by 26 articles

See all "Cited by" articles


    1. Postel-Vinay S, Vanhecke E, Olaussen KA, Lord CJ, Ashworth A, Soria JC. The potential of exploiting DNA-repair defects for optimizing lung cancer treatment. Nature reviews Clinical oncology. 2012;9:144–155. - PubMed
    1. Martin SA, Lord CJ, Ashworth A. Therapeutic targeting of the DNA mismatch repair pathway. Clinical cancer research : an official journal of the American Association for Cancer Research. 2010;16:5107–5113. - PubMed
    1. Plummer R. Perspective on the pipeline of drugs being developed with modulation of DNA damage as a target. Clinical cancer research. 2010;16:4527–4531. - PubMed
    1. Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature. 2001;411:366–374. - PubMed
    1. Abbotts R, Thompson N, Madhusudan S. DNA repair in cancer: emerging targets for personalized therapy. Cancer management and research. 2014;6:77–92. - PMC - PubMed

MeSH terms