Shuin T, Kondo K, Torigoe S, Kishida T, Kubota Y, Hosaka M, Nagashima Y, Kitamura H, Latif F, Zbar B
Department of Urology, Yokohama City University School of Medicine, Japan.
Cancer Res. 1994 Jun 1;54(11):2852-5.
We analyzed 47 primary sporadic human renal cell carcinomas (39 clear cell and 8 non-clear cell) for mutations of the von Hippel-Lindau (VHL) tumor suppressor gene using the polymerase chain reaction and single strand conformational polymorphism analysis of DNA. All of the positive cases in single strand conformational polymorphism analyses were further characterized by direct sequencing. Somatic mutations were detected in 22 (56%) of 39 clear cell renal carcinomas including 15 deletions, 3 insertions, 3 missense mutations, and 1 nonsense mutation. Nineteen of these mutations predicted to produce truncation of the VHL protein. These mutations mainly occurred in the last one-third region of exons 1, 2, and 3. In addition, loss of heterozygosity of the VHL gene was observed in 16 (84%) of 19 informative clear cell renal carcinomas. No somatic mutations were detected in 8 non-clear cell carcinomas. These results show that the VHL tumor suppressor gene is one of the major tumor suppressor genes in human renal cell carcinomas, especially in the clear cell subtype renal cell carcinoma. Clear cell carcinoma might be distinguished from other pathological types of renal cell carcinomas by molecular genetic techniques.
我们运用聚合酶链反应和DNA单链构象多态性分析，对47例原发性散发性人类肾细胞癌（39例透明细胞癌和8例非透明细胞癌）进行了von Hippel-Lindau（VHL）肿瘤抑制基因突变分析。单链构象多态性分析中的所有阳性病例均通过直接测序进一步鉴定。在39例透明细胞肾细胞癌中，有22例（56%）检测到体细胞突变，包括15例缺失、3例插入、3例错义突变和1例无义突变。其中19种突变预计会导致VHL蛋白截短。这些突变主要发生在外显子1、2和3的最后三分之一区域。此外，在19例信息充分的透明细胞肾细胞癌中，有16例（84%）观察到VHL基因杂合性缺失。8例非透明细胞癌未检测到体细胞突变。这些结果表明，VHL肿瘤抑制基因是人类肾细胞癌，尤其是透明细胞亚型肾细胞癌中的主要肿瘤抑制基因之一。透明细胞癌或许可通过分子遗传学技术与其他病理类型的肾细胞癌相区分。
