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

Oncogene volume 21, pages 5696–5703 (2002)Cite this article

Abstract

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 hMLH1 contribute to genomic instability and tumorigenesis in sporadic breast cancer.

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Acknowledgements

We thank Dr Michael Cibull for providing specimens for this study. This work was supported partially by grant GMC-98538 from the American Cancer Society and grant DAMD17-99-1-9246 from the Department of Defense (to G-M Li).

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  1. Hiroaki Murata

    Present address: Gastroenterology Division, Department of Internal Medicine and Therapeutics, Osaka University, Graduate School of Medicine, 2-2, Yamada-Oka, Suita-City, 565-0871, Osaka, Japan

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Markey Cancer Center, University of Kentucky Medical Center, Lexington, 40536, Kentucky, KY, USA

    Hiroaki Murata, Nada H Khattar, Yuna Kang, Liya Gu & Guo-Min Li

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Correspondence to Guo-Min Li.

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Murata, H., Khattar, N., Kang, Y. et al. Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability. Oncogene 21, 5696–5703 (2002). https://doi.org/10.1038/sj.onc.1205683

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