WT1基因突变和单核苷酸rs16754多态性在儿童急性髓细胞白血病的特征及临床意义的研究

发布时间：2018-05-12 05:10

本文选题：AML + WT1　；参考：《重庆医科大学》2012年硕士论文

【摘要】：目的：儿童AML的发病率较低，且尚没有关于我国儿童AML中WT1的突变及单核苷酸rs16754多态性分析及与预后相关性分析的报道，通过研究可以揭示WT1在我国儿童AML中的突变频率及与预后的关系，从而发现AML新的临床预后指标及发病途径。方法：通过对127例儿童AML初诊患者的骨髓进行血液病染色体、融合基因及FISH检查，根据SWOG把病例归纳为不同的预后风险级别，对其中的86例进行WT1基因突变分析及rs16754基因多态性的分析。结果：WT1基因突变率为20%，多发生于第7外显子与第9外显子，，WT1突变组与WT1野生组的总生存期与无病生存期没有差异。WT1第7外显子的rs16754多态性分析显示G是出现频率最多的等位基因，rs16754~(GG)与rs16754~(GA)频率分别为54.2%和37.5%。rs16754~(GG)病人的总的生存率（OS）及无病生存率（RFS）较rs16754~(GA/AA)病人高(p=0.020；p=0.025)；在CEBPA野生型的病例中，rs16754~(GG)病人OS（p=0.068）及RFS（p=0.044）较高于rs16754~(GA/AA)病人组。讨论：我们的数据表明，WT1的突变与疾病的预后没有关联。我们进一步研究揭示在第7外显子上rs16754等位基因多态性的改变，我们数据证明rs16754~(GG)病人的总的生存率（OS）及无病生存率（RFS）较rs16754~(GA/AA)病人高，这个趋势同样存在于CEBPA未突变的病例。
[Abstract]:Objective: the incidence of AML in children is relatively low, and there are no reports on the mutation of WT1 and the analysis of single nucleotide rs16754 polymorphism in Chinese children with AML and their correlation with prognosis. The mutation frequency of WT1 in Chinese children with AML and its relationship with prognosis can be revealed by the study, and a new clinical prognostic index and pathogenetic pathway of AML can be found. Methods: bone marrow samples from 127 children with AML were examined for hematological chromosomes, fusion genes and FISH. According to SWOG, the patients were classified into different prognostic risk levels. The mutation of WT1 gene and the polymorphism of rs16754 gene were analyzed in 86 cases. Results there was no difference between the total survival time and disease-free survival of WT1 gene mutation in exon 7 and exon 9 and in the wild group of WT1. The rs16754 polymorphism analysis of exon 7 of WT1 showed that G was the frequency of occurrence. The frequencies of rs16754 (GG) and rs16754 (GGG) were 54.2% and 37.5.rs16754 / GGG, respectively. The overall survival rate and disease-free survival rate (RFSs) were higher in rs16754 GGG and rs16754 GGG (rs16754 GGG) than in rs16754 GGG (rs16754 GGG) and RFSp0.044) compared with rs16754 GGG (rs16754 GGG) and RFSp0.044). Discussion: our data suggest that mutation of WT1 is not associated with disease prognosis. Our further study revealed a change in the rs16754 allele polymorphism at exon 7. Our data showed that the overall survival rate and disease-free survival rate of rs16754 / GG patients were higher than those of rs16754 / GA / AAA patients, and this trend was also present in patients without CEBPA mutation.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R733.7

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