肾母细胞瘤16q杂合性丢失及其临床意义

Loss of 16q heterozygosity in Wilms' tumor and its clinical importance

目的 探讨肾母细胞瘤 16 q杂合性丢失 (LOH)的频率及其与选择性病理临床参数的联系。方法 抽提 32例肿瘤组织的DNA及其正常组织DNA ,用 16q2 4区域微卫星多肽标记 ,PCR方法对 16 q2 4多肽序列扩增 ,聚丙烯酰胺凝胶电泳 ,行LOH分析。其结果与患儿年龄、性别、临床分期、组织学类型和复发、转移、死亡作统计分析。结果 年龄大于 2 4个月患儿LOH 16q明显增多 (P<0 .0 5 ) ;LOH 16 q发生于临床Ⅱ期或Ⅲ期 ,明显高于Ⅰ期 (P <0 .0 5 ) ,而Ⅱ、Ⅲ期之间无明显差别。LOH 16 q与性别、肿瘤组织类型无关 ;LOH 16 q阳性患儿死亡率是LOH 16q阴性患儿的 4倍。 结论 LOH 16 q多见于小儿肾母细胞瘤 ,检测小儿肾母细胞瘤LOH 16q有益于高危人群的分类。

Objective To search for the frequency of loss of 16q heterozygosity (LOH 16?q) and the relationship between LOH 16?q and selected pathoclinical parameters.Methods The study comprised 32 children (15 girls and 17 boys) aged from 2 months to 13 years (median 38 months), treated for unilateral Wilms' tumor in the years of 1994-1999. DNA was isolated from paraffin embedding specimen and paired normal tissue, and was prepared using the standard phenol chloroform extraction method. The methods involved the amplification of polymorphic sequences from the 16q24 region by polymerase chain reaction and separation of the products of amplification by polyacrylamide gel electrophoresis. The results were the subject of statistical analysis in relation to gender, age at first diagnosis, clinical stage, histological type, recurrences, metastases and death.Results Nine ( 28.1% ) cases showed LOH 16?q , including LOH of both alleles in one case. No LOH was found in 21( 61.9% ) cases and in 2 cases the results were non informative. The study revealed a lack of correlation between LOH 16?q and gender, however LOH 16?q was more common in children older than 24 months ( P < 0.05 ). LOH 16?q was more frequent in stage (CS) Ⅱ or Ⅲ tumors than in CS Ⅰ, but there were no difference in the occurrence of LOH 16?q and the histological type of tumor. However, LOH 16?q has been found four times as common in tumors from children who died than in tumors of children who survived ( P < 0.05 ).Conclusion LOH 16?q is seen in about 20-30% of Wilms' tumor with a poor prognosis in children.