Development of papillary renal cell tumours is associated with loss of Y-chromosome-specific DNA sequences.

Twenty-two papillary renal cell tumours were analysed by Southern hybridization using eight DNA probes from homologous regions of the X and Y chromosomes and two Y-chromosome-specific DNA probes. Sixteen of the 19 papillary renal cell tumours of male patients showed the loss of Y-chromosome-specific sequences. No loss of heterozygosity was detected in three tumours that developed in females. The frequency of loss of the Y chromosome was established in 50 non-papillary renal cell carcinomas as well. Only seven of the 31 non-papillary renal cell carcinomas obtained from male patients had lost the Y-chromosome-specific sequences, whereas no allelic loss was found in 19 non-papillary tumours obtained from female patients. Papillary renal cell tumours show a strong male preponderance (6:1) and loss of Y chromosome in 84 per cent of the cases, whereas non-papillary renal cell carcinomas show only a slight male preponderance (1.5:1) and the Y chromosome is lost in only 22 per cent of the cases. These data suggest that a tumour suppressor gene is localized at one of the homologous regions of the X and Y chromosomes, the homozygous inactivation of which is associated with the development of papillary renal cell tumours.