dWe have used differential-display FCR (DD-PCR) to compare renal-cell carcinoma (RCC) and normal kidney gene expression with the aim of identifying genes specifically associated with RCC. Using a modified DD-PCR approach, which was non-radioactive, quicker and simpler than the conventional method, 24 cDNA samples were clearly up- or downregulated in RCC tissue from 4 patients. Fourteen of these showed high similarity to a number of known genes. Eight of these cDNA clones were chosen for further analysis. These were a regulator of G-protein signalling (RGS-5), Notch-3, Na,K-ATPase a! subunit, HLA class II antigen, ETS-like protein, transforming growth factor P-stimulated clone (TSC-22), bladder cancer-related protein (BC10) and adipophilin. Semi-quantitative RT-PCR using specific primers to each of these genes confirmed differential expression in 67% to 83% of a further 12 RCC and normal kidney paired samples from 7 of the 8 cDNA clones. Northern analysis further confirmed the up-regulation in expression of RGS-5 and Notch-3 in RCC. Further characterisation of these differentially expressed genes should lead to a better understanding of the changes that occur at the molecular level during RCC development and progression. (C) 2000 Wiley-Liss, Inc.