Coleman W B, Esch G L, Borchert K M, McCullough K D, Reid L H, Weissman B E, Smith G J, Grisham J W
Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
Mol Carcinog. 1997 Aug;19(4):267-72. doi: 10.1002/(sici)1098-2744(199708)19:4<267::aid-mc8>3.0.co;2-9.
We previously demonstrated that a locus (or loci) linked to the D11S436 marker, which is within the approximately 6-Mb cen-p12 region of human chromosome 11, suppresses the tumorigenic potential of some rat liver epithelial tumor microcell hybrid (MCH) cell lines. To more precisely map this putative liver tumor suppressor locus, we examined 25 loci from human chromosome 11 in suppressed MCH cell lines. Detailed analysis of these markers revealed a minimal area of overlap among the suppressed MCH cell lines corresponding to the chromosomal region bounded by (but not including) microsatellite markers D11S1319 and D11S1958E and containing microsatellite markers D11S436, D11S554, and D11S1344. Direct examination of the kang ai 1 (KA/1) prostatic adenocarcinoma metastasis suppressor gene (which is closely linked to D11S1344) produced evidence suggesting that this locus was not responsible for tumor suppression in this model system. In addition, our data strongly suggested that the putative liver tumor suppressor locus was distinct from other known 11p tumor suppressor loci, including the multiple exotoses 2 locus (at 11p11.2-p12), Wilms' tumor 1 locus (at 11p13), and Wilms' tumor 2 locus (at 11p15.5). The results of this study significantly narrowed the chromosomal location of the putative liver tumor suppressor locus to a region of human 11p11.2-p12 that is approximately 950 kb. This advance forms the basis for positional cloning of candidate genes from this region and, in addition, identified a number of chromosomal markers that will be useful for determining the involvement of this locus in the pathogenesis of human liver cancer.
我们先前证明，与D11S436标记相关的一个（或多个）基因座可抑制某些大鼠肝上皮肿瘤微细胞杂交（MCH）细胞系的致瘤潜力，该标记位于人类11号染色体约6 Mb的着丝粒-p12区域内。为了更精确地定位这个假定的肝肿瘤抑制基因座，我们在受抑制的MCH细胞系中检测了来自人类11号染色体的25个基因座。对这些标记的详细分析揭示，在受抑制的MCH细胞系中存在一个最小重叠区域，该区域对应于由微卫星标记D11S1319和D11S1958E界定（但不包括）且包含微卫星标记D11S436、D11S554和D11S1344的染色体区域。对抗癌1（KA/1）前列腺癌转移抑制基因（其与D11S1344紧密连锁）的直接检测结果表明，该基因座在这个模型系统中不负责肿瘤抑制。此外，我们的数据强烈表明，假定的肝肿瘤抑制基因座与其他已知的11p肿瘤抑制基因座不同，包括多发性外生性骨疣2基因座（位于11p11.2 - p12）、威尔姆斯瘤1基因座（位于11p13）和威尔姆斯瘤2基因座（位于11p15.5）。这项研究的结果将假定的肝肿瘤抑制基因座的染色体定位显著缩小至人类11p11.2 - p12上一个约950 kb的区域。这一进展为从该区域进行候选基因的定位克隆奠定了基础，此外，还鉴定出了一些染色体标记，这些标记将有助于确定该基因座在人类肝癌发病机制中的作用。
