Mutational Analysis of the VHL Tumor Suppressor Gene in Sporadic Renal Cell Carcinoma

我们应用聚合酶链式反应-单链构象多态性分析和测序方法对47例散发性肾细胞癌进行了von Hippel-Lindau(VHL)抑癌基因的体细胞突变分析。47例中有22例发生基因内突变，其中缺失15例，插入3例，错义突变3例，无义突变1例。根据Thoenes的分类，这些突变仅在透明细胞型肾癌中观察到。这些突变中的任何一个都被预测会导致VHL蛋白的截断。此外，在19例信息性透明细胞肾癌中有16例观察到VHL基因杂合性缺失(LOH)。我们还在散发性中枢神经系统血管母细胞瘤中发现了VHL基因的体细胞突变。这些结果表明，VHL基因是透明细胞型肾癌和中枢神经系统血管母细胞瘤的主要抑癌基因之一。分子遗传学分析将为这些肿瘤的诊断提供有用的信息。

We analyzed 47 sporadic renal cell carcinomas for somatic mutations of the von Hippel-Lindau(VHL)tumor suppressor gene by PCR-SSCP and sequencing analyzes. Intragenic mutations were detected in 22 of 47 cases including 15 deeletions, 3 insertions, 3 missense mutations and 1 nonsense mutation. These mutations were observed exclusively in clear-cell type renal carcinomas according to the Thoenes' classification. Ninteen of these mutations predicted to produce truncation of the VHL protein. In addition loss of heterozygosity(LOH)of the VHL gene was observed in 16 of 19 informative clear-cell renal carcinomas. We also found somatic mutations of the VHL gene in sporadic central nervous system(CNS)hemangioblastomas. These results show that the VHL gene is one of the major tumor suppressor genes both in clear-cell type renal carcinomas and in CNS hemangioblastomas. Molecular genetic analyzes will provide useful informations for diagnosis of these tumors.