Somatic mutations of the von Hippel-Lindau disease gene in renal carcinomas occurring in patients with long-term dialysis

Background. Renal cell carcinoma (RCC) frequently occurs in patients with long-term dialysis. Long-term dialysis causes distinctive pathological changes in the kidney, which is known as acquired cystic disease of the kidney (ACDK). It is of great interest to know whether RCCs occurring in the dialytic kidneys harbour the same or similar mutations of the von Hippel-Lindau (VHL) gene as conventional dialysis-unrelated clear cell RCCs so often do. Methods. Renal cancer tissues (eight clear cell, two papillary, one Bellini duct and three of the so-called dialysis-specific renal carcinomas) from 13 patients undergoing long-term dialysis were examined for somatic mutations of the VHL disease gene. By means of laser capture microdissection, cancerous and surrounding non-cancerous renal tissues from dialytic patients were subjected to PCR-based direct sequencing of the VHL gene. Results. Direct forward and reverse sequencing showed that three tumours possessed VHL gene mutations (713delG, 500-504del5-bp and 709A > G). These three mutations were identified in clear cell carcinomas occurring in association with end-stage renal disease undergoing dialysis for 194, 147 and 125 months. None of the non-tumour tissues or other carcinoma tissues analysed, including dialysis-specific carcinoma, possessed VHL gene mutations. Conclusion. These results indicate that VHL tumour-suppressor gene mutation is involved in clear cell carcinoma in association with long-term dialysis. Mutation of the VHL gene was not found in any of the dialysis-specific RCCs studied herein.