Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability

被引:71
作者
Murata, H [1 ]
Khattar, NH [1 ]
Kang, Y [1 ]
Gu, LY [1 ]
Li, GM [1 ]
机构
[1] Univ Kentucky, Ctr Med, Dept Pathol & Lab Med, Markey Canc Ctr, Lexington, KY 40536 USA
关键词
hMSH2; hMLH1; microsatellite instability; hypermethylation; breast cancer;
D O I
10.1038/sj.onc.1205683
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Breast cancer is the most common cancer in women, but its pathogenesis is still unclear. Microsatellite instability (MSI) has been identified in breast cancer cells, suggesting an association with mismatch repair defects. To test this hypothesis, we investigated MSI, protein expression of hMSH2 and hMLH1, as well as genetic and epigenetic modifications of these two genes in 32 sporadic breast tumors. MSI was identified in 15 cases. Immunohistochemistry analysis revealed that all MSI cases but one had lower than normal expression of hMSH2 (nine cases), hMLH1 (12 cases), or both (seven cases). In tumors with MSI, both genetic and epigenetic modifications of these mismatch repair genes were also identified. Eight cases harbored mutations or polymorphisms in hMSH2 and hMLH1, and 10 exhibited hypermethylation in the promoter region of hMLH1. These results suggest that both genetic and epigenetic alterations of hMSH2 and especially of h-MLH1 contribute to genomic instability and tumorigenesis in sporadic breast cancer.
引用
收藏
页码:5696 / 5703
页数:8
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