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.
Copyright 2003 Wiley-Liss, Inc.