title: [Clinical significance of hypermethylation of DLC-1 gene in myelodysplastic syndrome patients and effects of decitabine on DLC-1 gene expression].
abstract: Objective:To detect the methylation status of DLC-1 gene in the patients with myelodysplastic syndrome(MDS), the effect of abnormal methylation of DLC-1 gene on the expression of DLC-1 gene, the clinical significance of methylation of DLC-1 gene in MDS patients, and the effect of decitabine on DLC-1 gene expression.Methods:A total of 43 MDS patients were treated in Fujian Medical University Union Hospital from 2013 to 2015. Methylation status of DLC-1 gene in MDS patients were detected by the methylation specific PCR(MSP). The expression of DLC-1 gene mRNA was determined with real-time fluorescence quantitative PCR(RTFQ-PCR). MDS patients were divided into 5 groups (very low-risk, low-risk, intermediate-risk, high-risk and very high-risk,n=0, 8, 7, 18, 10) according to WPSS classification. And the clinical significance of methylation of DLC-1 gene in patients with MDS were investigated. In order to investigate the change in gene methylation and expression of DLC-1 gene after treatment with decitabine, methylation statuses of DLC-1 gene in MDS patients before and after be treated with decitabine were detected by the bisulfite sequencing PCR(BSP). The expressions of DLC-1 gene mRNA of these patients were determined with RTFQ-PCR.Results:Hypermethylation of CpG island of DLC-1 gene was observed in 55.16%(22/43)MDS patients. The expressions of DLC-1 gene mRNA in methylation positive patients were significantly lower than that in methylation negative patients (0.32±0.06 vs 0.91±0.11)(P=0.008). For MDS patients, the DLC-1 methylation rate of intermediate-and high-risk patient was 21/35, which was significantly higher than that of low-risk patient(1/8,P=0.006). The methylation status of DLC-1 gene were monitored in 8 patients before and after treatment with the decitabine (decitabine 20 mg/m(2,) d1-d5/d28, more than 4 courses) , the methylation rate of DLC-1 gene dropped from 57.50%±5.11% to 14.13%±2.07% after treatment(P=0.010). The expression of DLC-1 gene increased after treatment with decitabine(0.67±0.08 vs 0.28±0.06,P=0.015).Conclusions:Methylation of DLC-1 gene is common in MDS patients and may be associated with poor prognosis. Decitabine may activate the expression of DLC-1 gene by demethylation, which may be one of the mechanisms for the treatment of patients with MDS.
authors.affiliation: Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Fu
authors.forename: H R
authors.initials: HR
authors.lastname: Zhou
authors.forename: J G
authors.initials: JG
authors.lastname: Yan
authors.forename: C J
authors.initials: CJ
authors.lastname: Chen
authors.forename: J Z
authors.initials: JZ
authors.lastname: Shen
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D020690:GTPase-Activating Proteins; D015870:Gene Expression; D006801:Humans; D009190:Myelodysplastic Syndromes; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins
chemical_list: C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine
keywords: DLC-1 gene; Decitabine; Epigenomics; Methylation; Myelodysplastic syndrome