title: Somatic von Hippel-Lindau disease gene mutation in clear-cell renal carcinomas associated with end-stage renal disease/acquired cystic disease of the kidney.
abstract: It has been documented that renal cell carcinomas (RCCs) occur frequently in patients treated with long-term dialysis, especially in cases of end-stage renal disease (ESRD)/acquired cystic disease of the kidney (ACDK). To address the molecular pathogenesis of ESRD/ACDK-associated RCCs, we examined 14 RCCs (7 clear-cell and 7 papillary carcinomas) in patients receiving dialysis for somatic mutations of the von Hippel-Lindau disease (VHL) gene as well as of the tyrosine kinase domain of the MET oncogene. Direct sequencing analyses revealed that three tumors exhibited VHL frameshifts (618delA, 386-395del10-bp, and 723-724insTC). One of the VHL mutated tumors showed additional loss of heterozygosity at the VHL gene locus. Histopathologic and clinical data demonstrated that the three tumors having VHL mutations were clear-cell RCCs occurring in ESRD with 55, 106, and 156 months of dialysis history, respectively. We did not find any tumors with mutations in the tyrosine kinase domain of the MET. These results demonstrated that the VHL tumor-suppressor gene is also involved in a subset of clear-cell RCCs occurring in ESRD/ACDK, as in the case of sporadic clear-cell RCCs. However, mutations of the MET oncogene could not be found in the seven ESRD/ACDK-associated papillary RCCs examined.
authors.affiliation: Department of Urology, Yokohama City University School of Medicine, Yokohama, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yao
authors.forename: Isao
authors.initials: I
authors.lastname: Ishikawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kishida
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagashima
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Kondo
authors.forename: Noboru
authors.initials: N
authors.lastname: Nakaigawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hosaka
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics*; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics* / Q000628:therapy; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000628:therapy; D007680:Kidney Neoplasms / Q000235:genetics*; D008025:Ligases / Q000235:genetics*; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D013997:Time Factors; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human