Analysis of multiple renal cell adenomas and carcinomas suggests allelic loss at 3p21 to be a prerequisite for malignant development.

Multiple renal cell tumours from three unrelated patients have been analysed for loss of heterozygosity of 3p, mutation of VHL, and chromosome 7 and 17 imbalances. Loss of 3p alleles is characteristic for clear cell type tumours and the combination of +7, +17 for chromophilic cell type tumours. Thus, we could classify adenomas and carcinomas of the three patients according to the genomic patterns of the tumours. Adenomas appeared to be mostly of the chromophilic cell type. In some adenomas, however, allelic losses of chromosome 3 were detected, pointing to a clear cell phenotype. Irrespective of showing loss or retention of the 3p25 region, none of the adenomas had a VHL mutation. Therefore, inactivation of VHL does not seem to be an early event in the development of renal cell tumours. Results of an analysis of regions of loss and retention of alleles of 3p markers in multiple tumours of the individual patients suggest that losses at either 3p25 or 3p12-p14 are associated with adenomas. Additional loss at 3p21 is most likely required to lead to development of a more malignant clear cell carcinoma.