ALLELIC LASS ON CHROMOSOMES 3P, 5Q AND 17P IN RENAL-CELL CARCINOMAS

Loss-of-heterozygosity (LOH) has been studied on 3p (von Hippel-Lindau gene locus), 5q and 17p (p53 gene locus) by a polymerase chain reacti on (PCR)-based strategy in 42 sporadic renal cell carcinomas (RCC). LO H at seven microsatellite loci on 5q was investigated because a tumor suppresser gene on 5q involved in the development and/or progression o f RCC has not yet been identified. LOH was found in seven (17%) RCC at single or multiple loci on 5q, 38% (11/29 informative cases) on 3p, a nd 6% (2/35 informative cases) on 17p. Replication error (RER) was pre sent in 10% (4/42) RCC at single or multiple loci. The minimum region of deletion on 5q to account for LOH was mapped to 5q31.1 (interferon regulatory factor-1; IRF-1 locus), where LOH was detected in 23% (6/26 informative cases). LOH on 3p and 5q occurred in both stage 2 and mor e advanced (stage 3 and 4) tumors at similar incidences (41 and 33% on 3p; and 24 and 22% on 5q, respectively), suggesting that LOH on these chromosomes is an early genetic event. All RCC exhibiting LOH on 3p o r 5q (IRF-1 locus) were the clear cell or the mixed clear and granular cell types. These findings suggest that LOH on 3p and 5q plays an imp ortant role in the genesis of clear cell RCC. In addition, only one tu mor exhibited LOH on both 3p and 5q, which suggests that LOH occurs no t sequentially but independently.