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Germline and Somatic Mutations in the Tyrosine Kinase Domain of the Met Proto-Oncogene in Papillary Renal Carcinomas

  1. Author:
    Schmidt, L.
    Duh, F. M.
    Chen, F.
    Kishida, T.
    Glenn, G.
    Choyke, P.
    Scherer, S. W.
    Zhuang, Z. P.
    Lubensky, I.
    Dean, M.
    Allikmets, R.
    Chidambaram, A.
    Bergerheim, U. R.
    Feltis, J. T.
    Casadevall, C.
    Zamarron, A.
    Bernues, M.
    Richard, S.
    Lips, C. J. M.
    Walther, M. M.
    Tsui, L. C.
    Geil, L.
    Orcutt, M. L.
    Stackhouse, T.
    Lipan, J.

  2. Author Address

    Schmidt L SAIC FREDERICK INTRAMURAL RES SUPPORT PROGRAM FREDERICK, MD 21702 USA NCI IMMUNOBIOL LAB FREDERICK CANC RES & DEV CTR FREDERICK, MD 21702 USA NIH GENET EPIDEMIOL BRANCH BETHESDA, MD 20892 USA NIH DEPT DIAGNOST RADIOL BETHESDA, MD 20892 USA HOSP SICK CHILDREN DEPT GENET TORONTO ON M5G 1X8 CANADA NCI PATHOL LAB NIH BETHESDA, MD 20892 USA NCI LAB GEN DIVERS FREDERICK CANC RES & DEV CTR FREDERICK, MD 21702 USA KAROLINSKA HOSP DEPT SURG S-10401 STOCKHOLM SWEDEN CREDIT VALLEY HOSP DEPT LAB MED MISSISSAUGA ON CANADA UNIV AUTONOMA BARCELONA INST BIOL FONAMENTAL E-08193 BARCELONA SPAIN HOSP COMARCAL SANTIAGO APOSTOL BURGOS SPAIN HOP NECKER ENFANTS MALAD LAB NEUROONCOL PARIS FRANCE UNIV UTRECHT HOSP UTRECHT NETHERLANDS NIH SURG BRANCH BETHESDA, MD 20892 USA UNIV HAMBURG KRANKENHAUS EPPENDORF D-2000 HAMBURG GERMANY UNIV MAINZ DEPT HEMATOL & ONCOL D-6500 MAINZ GERMANY INST PATHOL WUPPERTAL GERMANY VET AFFAIRS MINNEAPOLIS, MN 55362 USA VET AFFAIRS NORTHPORT, NY 11768 USA UNIV BASEL INST PATHOL BASEL SWITZERLAND
    1. Year: 1997
  2. Journal: Nature Genetics
    1. 16
    2. 1
    3. Pages: 68-73
  4. Type of Article: Article
  1. Abstract:

    Hereditary papillary renal carcinoma (HPRC) is a recently recognized form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumours(1-4). The pattern of inheritance of HPRC is consistent with autosomal dominant transmission with reduced penetrance. HPRC is histologically and genetically distinct from two other causes of inherited renal carcinoma, von Hippel-Lindau disease (VHL) and the chromosome translocation (3;8)(5-6). Malignant papillary renal carcinomas are characterized by trisomy of chromosomes 7, 16 and 17, and in men, by loss of the Y chromosome(7), Inherited and sporadic clear cell renal carcinomas are characterized by inactivation of both copies of the VHL gene by mutation, and/or by hypermethylation(8-11). We found that the HPRC gene was located at chromosome 7q31.1-34 in a 27-centimorgan (cM) interval between D7S496 and D7S1837. We identified missense mutations located in the tyrosine kinase domain of the MET gene in the germline of affected members of HPRC families and in a subset of sporadic Family: papillary renal carcinomas. Three mutations in the MET gene are located in codons that are homologous to those in c-kit and RET, proto-oncogenes that are targets of naturally-occurring mutations. The results suggest that missense mutations located in the MET proto-oncogene lead to constitutive activation of the MET protein and papillary renal carcinomas. [References: 41]

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