Genes encoding human caveolin‐1 and ‐2 are co‐localized to the D7S522 locus (7q31.1), a known fragile site (FRA7G) that is frequently deleted in human cancers

摘要

>The (CA)_n microsatellite repeat marker D7S522 is located on human chromosome 7q31.1 and is frequently deleted in a variety of human cancers, including squamous cell carcinomas of the head and neck, prostate cancers, 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 been proposed that an as yet unidentified tumor suppressor gene (or genes) is contained within or located in close proximity to this locus. However, the identity of the candidate tumor suppressor gene at the D7S522 locus remains unknown. Here, we show that the human genes encoding caveolins 1 and 2 are contained within the same human genomic BAC clones and co-localize to the q31.1-q31.2 region of human chromosome 7, as seen by FISH analysis. In addition, we determined the intron-exon boundaries of the human caveolin-1 and -2 genes. The human caveolin-1 gene contains three exons, while the human caveolin-2 gene contains two exons. Interestingly, the boundary of the last exon of the human caveolin-1 and caveolin-2 genes are analogous, suggesting that they arose through gene duplication at this locus. (CA)_n microsatellite repeat marker analysis of these caveolin genomic clones indicates they contain the marker D7S522 (located at 7q31.1), but not other microsatellite repeat markers tested. The close proximity of caveolins 1 and 2 to the D7S522 locus was independently confirmed by using a panel of MIT/Whitehead human STS markers that are known to map in the neighborhood of the D7S522 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, 16374–16381), we propose that the caveolin-1 gene may represent the candidate tumor suppressor gene at the D7S522 locus on human chromosome 7q31.1.