Smith D I, Huang H, Wang L
Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Foundation, 200 First Street, S.W., Rochester, MN 55905, USA.
Int J Oncol. 1998 Jan;12(1):187-96.
Chromosomal fragile sites are specific loci which are especially susceptible to forming gaps, breaks and rearrangements in metaphase chromosomes when cells are cultured under conditions that inhibit DNA replication. Fragile sites are grouped into two classes the 'rare' and the 'common' fragile sites, based on their frequency of occurrence and means of induction. The common fragile sites are apparently present as a constant feature in all individuals and their clinical significance is that they might predispose chromosomes to breakage and rearrangement during cancer development. The most frequently observed common fragile sites occur, in decreasing order, at 3p14.2 (FRA3B), 16q23 (FRA16D), 6q26 (FRA6E), 7q32 (FRA7H), and Xp22 (FRAXB). FRA3B has been of particular interest since it is the most active common fragile site, and is located in a chromosomal band that is frequently deleted in several solid tumors suggesting that a putative tumor suppressor gene resides there. In this review we describe our work on the characterization of FRA3B and the analysis of deletions in the FRA3B region in several different tumor-derived cell lines. We also describe our efforts to identify other common fragile sites and to determine the role that these sites play in tumor development.
染色体脆性位点是特定的基因座，当细胞在抑制DNA复制的条件下培养时，它们在中期染色体中特别容易形成间隙、断裂和重排。根据其出现频率和诱导方式，脆性位点分为两类：“罕见”脆性位点和“常见”脆性位点。常见脆性位点显然在所有个体中都是一种恒定特征，其临床意义在于它们可能使染色体在癌症发展过程中易于发生断裂和重排。最常观察到的常见脆性位点按出现频率从高到低依次位于3p14.2（FRA3B）、16q23（FRA16D）、6q26（FRA6E）、7q32（FRA7H）和Xp22（FRAXB）。FRA3B一直备受关注，因为它是最活跃的常见脆性位点，且位于一个在几种实体瘤中经常缺失的染色体带区，这表明一个假定的肿瘤抑制基因位于那里。在这篇综述中，我们描述了我们对FRA3B的特征描述以及对几种不同肿瘤来源细胞系中FRA3B区域缺失情况的分析工作。我们还描述了我们为识别其他常见脆性位点以及确定这些位点在肿瘤发展中所起作用而做出的努力。
