Familial clear cell renal cell carcinoma (FCRC) : clinical features and mutation analysis of the VHL, MET, and CUL2 candidate genes

• Published in: Journal of medical genetics 2000-05, Vol.37 (5), p.348-353
• Main Authors: WOODWARD, E. R, CLIFFORD, S. C, ASTUTI, D, AFFARA, N. A, MAHER, E. R
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Carrier Proteins - genetics; Cell Cycle Proteins - genetics; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 7; Cullin Proteins; Female; Genetic Linkage; Humans; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Kidneys; Ligases; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Original; Polymorphism, Single-Stranded Conformational; Proteins - genetics; Proto-Oncogene Proteins c-met - genetics; Tumor Suppressor Proteins; Tumors of the urinary system; Ubiquitin-Protein Ligases; Von Hippel-Lindau Tumor Suppressor Protein
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.37.5.348

Familial renal cell carcinoma (RCC) is genetically heterogeneous. Genetic predisposition to clear cell RCC (CCRCC) is a major feature of von Hippel-Lindau (VHL) disease (MIM 193300) and has rarely been associated with chromosome 3 translocations. In addition, familial papillary (non-clear cell) RCC may result from germline mutations in the MET proto-oncogene (MIM 164860). However, rare kindreds with familial CCRCC (FCRC) not linked to the VHL tumour suppressor gene have been described suggesting that further familial RCC susceptibility genes exist. To investigate the genetic epidemiology of FCRC, we undertook a clinical and molecular study of FCRC in nine kindreds with two or more cases of CCRCC in first degree relatives. FCRC was characterised by an earlier age at onset (mean 47.1 years, 52% of cases