Methylation and expression of mismatch repair gene human mutS homolog 2 in myelodysplastic syndromes

Liu,Xiaoliu; Liu,Sufang; Lei,Jian; Zou,Lixin; Xiao,Le; Zhang,Guangsen

doi:10.3892/etm.2017.5402

Methylation and expression of mismatch repair gene human mutS homolog 2 in myelodysplastic syndromes

Authors:
- Xiaoliu Liu
- Sufang Liu
- Jian Lei
- Lixin Zou
- Le Xiao
- Guangsen Zhang
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Affiliations: Department of Hematology, The Affiliated Changsha Hospital, Hunan Normal University, Changsha, Hunan 410006, P.R. China, Division of Hematology, Institute of Molecular Hematology, The Second Xiang‑Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Pathology, The Affiliated Tumor Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: October 30, 2017 https://doi.org/10.3892/etm.2017.5402
Pages: 500-505

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Abstract

As a highly heterogeneous disease, the pathogenesis of myelodysplastic syndrome (MDS) has not been well defined. In the present study, human mutS homolog 2 (hMSH2) promoter methylation was detected with methylation‑specific polymerase chain reaction (PCR). The function of hMSH2 was analyzed by microsatellite instability (MSI) detection of BAT‑26, and hMSH2 expression was evaluated using reverse transcription‑quantitative PCR in 60 patients with MDS. The results revealed methylation of the hMSH2 promoter in 18 patients with MDS who have an overall prevalence of 30% (95% confidence interval, 18.4‑41.6%). Among the patients with hMSH2 methylation, 2 patients exhibited MSI. It was demonstrated that hMSH2 promoter methylation was increased in MDS with an increase in Revised International Prognostic Scoring System (IPSS‑R) risk, and patients with higher hMSH2 promoter methylation had shorter overall survival by Kaplan‑Meier analysis (P=0.011). In addition, it was also observed that decreased hMSH2 mRNA expression was associated with high IPSS‑R risk group (high/very high vs. intermediate, P=0.003), and hMSH2 mRNA expression in CD34 positive bone marrow cells was lower compared with that in CD34 negative cells of patients with MDS (P=0.029). Methylation of hMSH2 may be valuable for prognostic evaluation and progression prediction of MDS. Furthermore, hMSH2 may serve a key function in the pathogenesis and prognosis of MDS.

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