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Detailed molecular cytogenetic characterisation of the myeloid cell line U937 reveals the fate of homologous chromosomes and shows that centromere capture is a feature of genome instability
Molecular Cytogenetics ( IF 1.3 ) Pub Date : 2020-12-14 , DOI: 10.1186/s13039-020-00517-y
Ruth N. MacKinnon , Joanne Peverall , Lynda J. Campbell , Meaghan Wall

The U937 cell line is widely employed as a research tool. It has a complex karyotype. A PICALM-MLLT10 fusion gene formed by the recurrent t(10;11) translocation is present, and the myeloid common deleted region at 20q12 has been lost from its near-triploid karyotype. We carried out a detailed investigation of U937 genome reorganisation including the chromosome 20 rearrangements and other complex rearrangements. SNP array, G-banding and Multicolour FISH identified chromosome segments resulting from unbalanced and balanced rearrangements. The organisation of the abnormal chromosomes containing these segments was then reconstructed with the strategic use of targeted metaphase FISH. This provided more accurate karyotype information for the evolving karyotype. Rearrangements involving the homologues of a chromosome pair could be differentiated in most instances. Centromere capture was demonstrated in an abnormal chromosome containing parts of chromosomes 16 and 20 which were stabilised by joining to a short section of chromosome containing an 11 centromere. This adds to the growing number of examples of centromere capture, which to date have a high incidence in complex karyotypes where the centromeres of the rearranged chromosomes are identified. There were two normal copies of one chromosome 20 homologue, and complex rearrangement of the other homologue including loss of the 20q12 common deleted region. This confirmed the previously reported loss of heterozygosity of this region in U937, and defined the rearrangements giving rise to this loss. Centromere capture, stabilising chromosomes pieced together from multiple segments, may be a common feature of complex karyotypes. However, it has only recently been recognised, as this requires deliberate identification of the centromeres of abnormal chromosomes. The approach presented here is invaluable for studying complex reorganised genomes such as those produced by chromothripsis, and provides a more complete picture than can be obtained by microarray, karyotyping or FISH studies alone. One major advantage of SNP arrays for this process is that the two homologues can usually be distinguished when there is more than one rearrangement of a chromosome pair. Tracking the fate of each homologue and of highly repetitive DNA regions such as centromeres helps build a picture of genome evolution. Centromere- and telomere-containing elements are important to deducing chromosome structure. This study confirms and highlights ongoing evolution in cultured cell lines.

中文翻译:

髓样细胞系U937的详细分子细胞遗传学特征揭示了同源染色体的命运,并表明着丝粒捕获是基因组不稳定的特征

U937细胞系被广泛用作研究工具。它具有复杂的核型。存在由复发性t(10; 11)易位形成的PICALM-MLLT10融合基因,并且20q12处的髓样共同缺失区已从其近三倍体核型中丢失。我们对U937基因组重组进行了详细的调查,包括20号染色体重排和其他复杂的重排。SNP阵列,G带和多色FISH鉴定了不平衡和平衡重排产生的染色体区段。然后,通过有针对性地使用靶向中期FISH来重建包含这些区段的异常染色体的组织。这为进化的核型提供了更准确的核型信息。在大多数情况下,可以区分涉及染色体对同源物的重排。在一个异常染色体中证实了着丝粒捕获,该异常染色体包含16和20号染色体的一部分,这些染色体通过与包含11个着丝粒的染色体的一小段相连而得以稳定。这增加了着丝粒捕获的例子的数量,这在复杂的核型中是很常见的,在复杂的染色体核型中,重排染色体的着丝粒被识别。一个染色体20个同源物有两个正常拷贝,另一个同源物的复杂重排包括丢失20q12共同缺失区。这证实了先前报道的U937中该区域杂合性的丧失,并确定了引起这种丧失的重排。着丝粒捕获 由多个片段拼凑而成的稳定染色体可能是复杂核型的共同特征。但是,直到最近才意识到这一点,因为这需要仔细鉴定异常染色体的着丝粒。此处介绍的方法对于研究复杂的重组基因组(例如由染色质产生的基因组)具有无价的价值,并且比仅通过微阵列,核型分析或FISH研究可获得的图像更完整。SNP阵列用于此过程的一个主要优点是,当染色体对存在多个重排时,通常可以区分两个同源物。追踪每个同源物和高度重复的DNA区域(如着丝粒)的命运有助于建立基因组进化图景。含着丝粒和端粒的元素对于推导染色体结构很重要。这项研究证实并强调了培养细胞系的持续进化。
更新日期:2020-12-14
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