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

散发性肾细胞癌VHL抑癌基因突变分析

• 批准号: 06671605
• 负责人: YAO Masahiro
• 金额: $ 1.34万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671605/
• 关键词: carcinoma; rsnal cell; VHL; tumor suppressor gene

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.

我们通过 PCR-SSCP 和测序分析，分析了 47 例散发性肾细胞癌的 von Hippel-Lindau (VHL) 肿瘤抑制基因的体细胞突变。 47例中有22例检测到基因内突变，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 分类，这些突变仅在透明细胞型肾癌中观察到。其中 19 个突变预计会产生 VHL 蛋白的截短。此外，在 19 例信息性透明细胞肾癌中的 16 例中观察到 VHL 基因杂合性丢失 (LOH)。我们还在散发性中枢神经系统（CNS）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CNS血管母细胞瘤中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。

项目成果

Taro Shuin et al.: "Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas" Cancer Research. 54. 2852-2855 (1994)

Taro Shuin 等人：“原发性人肾细胞癌中 von Hippel-Lindau 肿瘤抑制基因的频繁体细胞突变和杂合性丧失”癌症研究。

Shuin T.et al.: "Frequent somatic mutations and Loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas" Cancer Research. 54. 2852-2855 (1994)

Shuin T.等人：“原发性人肾细胞癌中 von Hippel-Lindau 肿瘤抑制基因的频繁体细胞突变和杂合性丢失”癌症研究。

Shuin T.et al.: "Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor gene in primary human renal cell carcinomas." Cancer Research. 54-10. 2852-2855 (1994)

Shuin T.等人：“原发性人肾细胞癌中 von Hippel-Lindau 肿瘤抑制基因的频繁体细胞突变和杂合性丧失。”

Kanno H.et al.: "Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central nervous system hemangioblastomas." Cancer Research. 54-18. 4845-4847 (1994)

Kanno H.等人：“散发性中枢神经系统血管母细胞瘤中 von Hippel-Lindau 肿瘤抑制基因的体细胞突变。”

Kanno M.et al.: "Somatic mutations of the von Hippel-Lindau tumor suppressor gene in sporadic central neurons system hemangioblastomas" Cancer Research. 54. 4845-4847 (1994)

Kanno M.等人：“散发性中枢神经元系统血管母细胞瘤中 von Hippel-Lindau 肿瘤抑制基因的体细胞突变”癌症研究。