Engelman J A, Zhang X L, Lisanti M P
Department of Molecular Pharmacology and the Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
FEBS Lett. 1998 Oct 9;436(3):403-10. doi: 10.1016/s0014-5793(98)01134-x.
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.
（CA）n微卫星重复标记D7S522位于人类7号染色体的7q31.1区域，在多种人类癌症中经常缺失，包括头颈部鳞状细胞癌、前列腺癌、肾细胞癌、卵巢腺癌、结肠癌和乳腺癌。此外，D7S522跨越FRA7G，这是人类7号染色体上一个已知的常见脆性位点。基于这些研究，有人提出在这个基因座内或其附近存在一个尚未确定的肿瘤抑制基因（或多个基因）。然而，D7S522基因座处候选肿瘤抑制基因的身份仍然未知。在这里，我们表明，编码小窝蛋白1和2的人类基因包含在相同的人类基因组BAC克隆中，并且通过荧光原位杂交（FISH）分析发现它们共定位于人类7号染色体的q31.1 - q31.2区域。此外，我们确定了人类小窝蛋白1和2基因的内含子 - 外显子边界。人类小窝蛋白1基因包含三个外显子，而人类小窝蛋白2基因包含两个外显子。有趣的是，人类小窝蛋白1和小窝蛋白2基因最后一个外显子的边界相似，表明它们是通过该基因座处的基因复制产生的。对这些小窝蛋白基因组克隆进行的（CA）n微卫星重复标记分析表明，它们包含标记D7S522（位于7q31.1），但不包含所测试的其他微卫星重复标记。通过使用一组已知定位于D7S522基因座附近的麻省理工学院/怀特黑德人类STS标记，独立证实了小窝蛋白1和2与D7S522基因座的紧密接近性。由于先前已表明小窝蛋白1具有转化抑制活性（科尔斯克，A.J.，巴尔的摩，D.和M.P.利桑蒂（1995年）《美国国家科学院院刊》92，1381 - 1385；恩格尔曼，J.A.等人（1997年）《生物化学杂志》272，16374 - 16381），我们提出小窝蛋白1基因可能代表人类7号染色体7q31.1区域D7S522基因座处的候选肿瘤抑制基因。
