The characterization of the common fragile site FRA16D and its involvement in multiple myeloma translocations
The characterization of the common fragile site FRA16D and its involvement in multiple myeloma translocations
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DOI：
10.1006/geno.2000.6321
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发表时间：
2000-10-01
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：
Krummel, KA;Roberts, LR;Smith, DI
当细胞在特定的培养条件下生长时，脆性位点表现为中期染色体上的断裂、缺口或去致密化。断裂是非随机的，出现在整个哺乳动物基因组中确定的保守位置。常见的脆弱部位，顾名思义，几乎存在于所有的个体中。随着三个常见的脆性位点的克隆，它们的表达机制和作用，如果有的话，他们在人类疾病中发挥的作用仍然不清楚。我们已经在第二个最活跃的常见脆性位点FRA 16 D（16q23.2）上组装了>1 Mb的BAC重叠群。我们荧光标记了这些BAC，并将它们用作来自阿非迪霉素诱导的淋巴细胞的中期分裂相上的探针，并证明FRA 16 D解凝聚/断裂发生在至少1 Mb的区域上。因此，这是迄今为止克隆的最大的常见脆性位点。在FRA 16 D内映射的微卫星标记物显示在前列腺、乳腺和卵巢肿瘤中非常高的丢失，表明在该脆弱位点内的丢失可能在这些肿瘤的发展或进展中是重要的。此外，在高达25%的多发性骨髓瘤（MM）中观察到常见的t（14 q32; 16 q23）易位。我们将四个这样的克隆t（14;16）MM断裂点定位在FRA 16 D区域内。这项工作进一步表明，常见的脆性位点可能在癌症发展中发挥重要作用。(C)北京大学出版社.
Fragile sites appear as breaks, gaps, or decondensations on metaphase chromosomes when cells are grown under specific culture conditions. The breaks are nonrandom, appearing in defined, conserved locations throughout the mammalian genome. Common fragile sites, as their name implies, are present in virtually all individuals. With three common fragile sites cloned, their mechanism of expression and the role, if any, they play in human disease are still unclear. We have assembled a BAC contig of >1 Mb across the second most active common fragile site, FRA16D (16q23.2), We fluorescently labeled these BACs and used them as probes on metaphases from aphidicolin-induced lymphocytes and demonstrated that FRA16D decondensation/breakage occurs over a region of at least 1 Rib. Thus, this is the largest common fragile site cloned to date. Microsatellite markers that map within FRA16D show a very high loss in prostate, breast, and ovarian tumors, indicating that loss within this fragile site may be important in the development or progression of these tumors. In addition, a common t(14q32; 16q23) translocation is observed in up to 25% of all multiple myelomas (MM). We localized four of four such cloned t(14;16) MM breakpoints within the FRA16D region. This work further demonstrates that the common fragile sites may play an important role in cancer development. (C) 2000 Academic Press.