急性淋巴细胞白血病6q16.3微卫星DNA缺失及临床相关性研究

Study of the allelic loss mapping on 6q16.3 and the clinical significance on acute lymphoblastic leukemia in children

目的定位儿童急性淋巴细胞白血病(ALL)杂合性缺失(LOH)的集中区,探讨新的肿瘤抑制基因及与临床相关性。方法取6q16.3的15个微卫星,利用聚合酶链反应-变性凝胶电泳-银染技术分析儿童ALL等位基因LOH的情况,进行生物信息学分析;探讨与临床预后因素的相关性。结果至少一个位点的LOH率为32.7%,D6S1709-D6S1028及D6S2160-D6S1580是集中高频缺失区,早期复发病例的LOH率高于无早期复发病例;谷氨酸受体6基因(GRIK2)为一有力的候选抑癌基因;两个区域有可能代表新基因的表达序列标签12个;LOH与白细胞总数、病态细胞数、核型分析、早期复发及免疫分型有相关性。结论D6S1709-D6S1028和D6S2160-D6S1580为目前国内外所确定的最精确缺失区,可能存在一个或数个肿瘤抑制基因,6q16.3LOH的发生与ALL预后有一定关系。

Objectives To locate the concentrate area of loss of heterozygosity （LOH） in children with acute lymphoblastic leukemia, and explore the new tumor suppressor gene and its clinical significance. Methods LOH was analyzed with PCR, denaturation gel electrophoresis, silver-staining, and 15 microsatellite markers mapping on 6q16.3. The bioinformation of LOH was analyzed to explore the clinical correlation between LOH and prognosis. Results The frequency of LOH at least at one locus on 6q16.3 was 32.7%. The higher frequency of LOH was observed in two regions of D6S1709-D6S1028 and D6S2160-D6S1580 at 6q16.3. The frequency of LOH in patients with relapse was higher than those without relapse. GRIK2 is a powerful tumor suppressor candidate gene. There were 12 ESTs that might carry out new antioncogene in the two areas. The patients with LOH at 6q had higher WBC counts, blast cells percentage, relapse rate, chromosomal aberration and immune dysfunction. Conclusions D6S1709-D6S1028 and D6S2160-D6S1580 are two regions of minimums deletion on 6q16.3 where tumor suppressor gene may exist. The LOH on 6q16.3 might be a prognostic index of children with ALL.