原发性散发性肾透明细胞癌患者癌组织中抑癌基因VHL突变的研究

Frequent somatic mutations of the von Hippel-Lindau tumor suppressor gene in primary sporadic human renal clear cell carcinomas

目的 探讨国人原发性散发性肾透明细胞癌中VHL抑癌基因突变及其意义。方法 采用聚合酶链反应及单链构像多态性分析 (PCR SSCP)和测序等方法 ,分析了 2 0例原发性散发性肾透明细胞癌中VonHippel Lindau(VHL)抑癌基因突变的情况。结果 2 0例癌组织中 11例有VHL基因突变 ,突变率为 5 5 %。这些突变主要发生在第 1,2 ,3号外显子的后 1/ 3区 ,其中 6例缺失 ,2例插入 ,3例误义突变。结论 国人原发性散发性肾透明细胞癌中存在VHL基因的突变。VHL基因可作为临床诊断指标 ,并可望成为肾透明细胞癌基因治疗的重要目的基因。

Objective To investigate the mutation of Von Hippel-Lndau (VHL) tumor suppressor gene in patients with primary sporadic human renal cell carcinoma (RCC). Methods DNA samples from 20 primary sporadic renal clear carcinoma patients were analyzed by polymerase chain reaction, single strand conformational polymorphism analyses (PCR-SSCP) and direct sequencing. Results Somatic mutations of the VHL gene were detected in 11 (55%) of the 20 clear cell renal carcinomas, including 6 deletions, 2 insertions, and 3 missense mutations. These mutations mainly occurred in the last one-third region of exon 1, 2 and 3 of the VHL gene. Conclusion The VHL gene may frequently mutate in Chinese patients with primary sporadic renal clear cell carcinoma. The VHL gene may be useful as a marker gene for the diagnosis of RCC and as a target gene for molecular therapy.