Wang N D, Testa J R, Smith D I
Department of Molecular Biology and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201.
Genomics. 1993 Aug;17(2):341-7. doi: 10.1006/geno.1993.1330.
The constitutive 3p14.2 fragile site is the most highly inducible fragile site in the human genome. This locus may predispose chromosome 3 to specific losses due to deletions and translocations that have been associated with several malignancies, including hereditary renal cell carcinoma. Using aphidicolin concentrations of 0.4 and 4.0 microM, we have generated and isolated 23 and 22 respective somatic cell hybrids that contain chromosome 3 short-arm breaks. The breakpoints in these hybrids have been localized with numerous chromosome 3 markers. We have observed that at the low aphidicolin dose, chromosome-3 breaks cluster within the 3p14.2 region, whereas at the high aphidicolin dose, two new loci, one within 3p14.1 and the other near the centromere, become predominantly affected. Our studies have failed to differentiate any of the 3p14.2 breakpoints from each other or from the t(3;8)(p14.2;q24.13) familial renal cell carcinoma translocation breakpoint, suggesting that the fragile site may have played a role in the generation of this balanced translocation. The resulting somatic cell hybrids generated from this work have refined the marker localizations within 3p13-p21.1 and should facilitate the physical characterization of this interesting region.
组成型3p14.2脆性位点是人类基因组中最易诱导的脆性位点。由于与包括遗传性肾细胞癌在内的几种恶性肿瘤相关的缺失和易位，该基因座可能使3号染色体易发生特定缺失。使用浓度为0.4和4.0微摩尔的阿非科林，我们分别产生并分离出了23个和22个含有3号染色体短臂断裂的体细胞杂种。这些杂种中的断点已通过多种3号染色体标记进行了定位。我们观察到，在低阿非科林剂量下，3号染色体断裂聚集在3p14.2区域内，而在高阿非科林剂量下，两个新的基因座，一个在3p14.1内，另一个靠近着丝粒，成为主要受影响的区域。我们的研究未能区分3p14.2的任何断点彼此之间或与t(3;8)(p14.2;q24.13)家族性肾细胞癌易位断点之间的差异，这表明脆性位点可能在这种平衡易位的产生中发挥了作用。这项工作产生的体细胞杂种完善了3p13-p21.1内的标记定位，并应有助于对这个有趣区域进行物理表征。
