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

• Project/Area Number: 06671605
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: Yokohama City University
• Principal Investigator: YAO Masahiro Yokohama City University School of medicine, Fuculty Staff, 医学部, 助手 (00260787)
• Co-Investigator(Kenkyū-buntansha): HOSAKA Masahiko Yokohama City University School of medicine, Professor, 医学部, 教授 (30106330) ; KUBOTA Yoshinobu Yokohama City University School of medicine, Associate Professor, 医学部, 助教授 (10106312)
• Project Period (FY): 1994 – 1995
• Project Status: Completed (Fiscal Year 1995)
• Budget Amount: ¥2,100,000 (Direct Cost: ¥2,100,000); Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
• Keywords: carcinoma / rsnal cell / VHL / tumor suppressor gene

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Taro Shuin et al.: "Frequent somatic mutations and loss of heterozygosity of the von Hippel-Lindau tumor suppressor in primary human renal cell carcinomas" Cancer Research. 54. 2852-2855 (1994)
• [Publications] 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)