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

被引：75
作者：
Gao, Dan [1 ,2 ]
Herman, James G. [3 ]
Guo, Mingzhou [1 ]
机构：
[1] Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing 100853, Peoples R China
[2] Nankai Univ, Coll Med, Tianjin 300071, Peoples R China
[3] Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, Pittsburgh, PA USA
来源：
ONCOTARGET | 2016年 / 7卷 / 24期
基金：
美国国家科学基金会;
关键词：
DNA methylation; DNA damage repair; MGMT; synthetic lethality; PARP inhibitor; SQUAMOUS-CELL CARCINOMA; NUCLEOTIDE EXCISION-REPAIR; SPORADIC BREAST-CANCER; NONPOLYPOSIS COLORECTAL-CANCER; MGMT PROMOTER METHYLATION; PERIPHERAL-BLOOD DNA; MISMATCH-REPAIR; OVARIAN-CANCER; MICROSATELLITE INSTABILITY; LUNG-CANCER;
D O I：
10.18632/oncotarget.7949
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：37331 / 37346
页数：16
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