CYTOGENETIC AND FLUORESCENCE IN-SITU HYBRIDIZATION STUDIES ON SPORADIC AND HEREDITARY TUMORS ASSOCIATED WITH VON HIPPEL-LINDAU SYNDROME (VHL)

We performed cytogenetic and fluorescence in situ hybridization (FISH) studies on 29 sporadic or familial tumors associated with von Hippel- Landau disease. Four of five renal cell carcinomas with detectable alt erations showed clones with chromosome 3 alterations. These changes le d to loss of genetic material visible with cytogenetic resolution: eit her an unbalanced translocation involving 3p or loss of a whole homolo g 3, resulting in monosomy of 3p. We have previously mapped the VHL ge ne to chromosomal region 3p25-p26. We applied FISH using the single co py probes cA233 and cA479, sequences close to the VHL gene, in a searc h for submicroscopic deletions of 3p. Use of FISH with differentially labeled probes indicated cA479 to be distal to cA233, but both were lo cated within bands 3p25-26. FISH with single copy probes for interphas e cytogenetics detected four subclones with deletions in the VHL regio n in 8/22 tumors, including four tumors which appeared cytogenetically normal. FISH proved to be a powerful tool in tumor genetic studies, e specially helpful in detecting tumor subclones in benign and slowly gr owing tumors.