Determination of the specificity of aphidicolin-induced breakage of the human 3p14.2 fragile site.
Determination of the specificity of aphidicolin-induced breakage of the human 3p14.2 fragile site.
复制标题
确定阿非迪霉素诱导的人类 3p14.2 脆弱位点断裂的特异性。
DOI：
10.1006/geno.1993.1330
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发表时间：
1993
期刊：
影响因子：
4.4
通讯作者：
Smith,DI
中科院分区：
文献类型：
--
作者：
Wang,ND;Testa,JR;Smith,DI
组成型3p14.2脆弱位点是人类基因组中最易诱导的脆弱位点。该位点可能使3号染色体因缺失和易位而发生特异性损失，这些缺失和易位与包括遗传性肾细胞癌在内的几种恶性肿瘤有关。在浓度为0.4 μM和4.0 μM的条件下，我们分别获得了23和22个含有3号染色体短臂断裂的体细胞杂交种。这些杂交种的断点已经用许多3号染色体标记定位。我们观察到，在低剂量下，3号染色体断裂聚集在3p14.2区域内，而在高剂量下，两个新的位点，一个在3p14.1区域内，另一个靠近着丝粒，主要受到影响。我们的研究未能区分任何一个3p14.2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，这表明脆弱位点可能在这种平衡易位的产生中发挥了作用。由此产生的体细胞杂交种细化了3p13-p21.1内的标记定位，并有助于对这一有趣区域的物理表征。
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 μM, 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.