GENES ENCODING HUMAN CAVEOLIN-1 AND CAVEOLIN-2 ARE CO-LOCALIZED TO THE D7S522 LOCUS (7Q31.1), A KNOWN FRAGILE SITE (FRA7G) THAT IS FREQUENTLY DELETED IN HUMAN CANCERS

The (CA), microsatellite repeat marker D7S522 is located on human chro mosome 7q31.1 and is frequently deleted in a variety of human cancers, including squamous cell carcinomas of the head and neck, prostate can cers, renal cell carcinomas, ovarian adenocarcinomas, colon carcinomas , and breast cancers. In addition, D7S522 spans FRA7G? a known common fragile site on human chromosome 7, Based on these studies, it has bee n proposed that an as yet unidentified tumor suppressor gene (or genes ) is contained within or located in close proximity to this locus. How ever, the identity of the candidate tumor suppressor gene at the D7S52 2 locus remains unknown. Here, we show that the human genes encoding c aveolins 1 and 2 are contained within the same human genomic BAC clone s and co-localize to the q31.1-q31.2 region of human chromosome 7, as seen by FISH analysis, In addition, we determined the intronexon bound aries of the human caveolin-1 and -2 genes, The human caveolin-1 gene contains three exons, while the human caveolin-2 gene contains two exo ns, Interestingly, the boundary of the last exon of the human caveolin -1 and caveolin-2 genes are analogous, suggesting that they arose thro ugh gene duplication rat this locus, (CA), microsatellite repeat marke r analysis of these caveolin genomic clones indicates they contain tbe marker D7S522 (located at 7q31,1), but not other microsatellite repea t markers tested. The close proximity of caveolins 1 and 2 to the D7S5 22 locus was independently confirmed by using a panel of MIT/Whitehead human STS markers that are known to map in the neighborhood of the D7 S522 locus. As it has been previously shown that caveolin 1 possesses transformation suppressor activity (Koleske, A.J,, Baltimore, D, and M ,P. Lisanti (1995) Proc, Natl, Acad. Sci. USA 92, 1381-1385; Engelman, J.A. et al. (1997) J, Biol, Chem, 272, 1637-16381), we propose that t he caveolin-1 gene may represent the candidate tumor suppressor gene a t the D7S522 locus on human chromosome 7q31.1, (C) 1998 Federation of European Biochemical Societies.