PDF(Pubmed)
Abstract：
Standard cytogenetic techniques (chromosomal banding analysis-CBA, and fluorescence in situ hybridization-FISH) show limits in characterizing complex chromosomal rearrangements and structural variants arising from two or more chromosomal breaks. In this study, we applied optical genome mapping (OGM) to fully characterize two cases of complex chromosomal rearrangements at high resolution. In case 1, an acute myeloid leukemia (AML) patient showing chromothripsis, OGM analysis was fully concordant with classic cytogenetic techniques and helped to better refine chromosomal breakpoints. The OGM results of case 2, a patient with non-Hodgkin lymphoma, were only partially in agreement with previous cytogenetic analyses and helped to better define clonal heterogeneity, overcoming the bias related to clonal selection due to cell culture of cytogenetic techniques. In both cases, OGM analysis led to the identification of molecular markers, helping to define the pathogenesis, classification, and prognosis of the analyzed patients. Despite extensive efforts to study hematologic diseases, standard cytogenetic methods display unsurmountable limits, while OGM is a tool that has the power to overcome these limitations and provide a cytogenetic analysis at higher resolution. As OGM also shows limits in defining regions of a repetitive nature, combining OGM with CBA to obtain a complete cytogenetic characterization would be desirable.
摘要：
标准细胞遗传学技术(染色体显带分析-CBA，和荧光原位杂交-FISH）在表征复杂的染色体重排和由两个或多个染色体断裂引起的结构变体方面显示出局限性。在这项研究中,我们应用光学基因组作图（OGM）以高分辨率完全表征了两个复杂的染色体重排病例。在病例1中，一名急性髓细胞性白血病（AML）患者出现染色体异常，OGM分析与经典的细胞遗传学技术完全一致，并有助于更好地改善染色体断点。2例非霍奇金淋巴瘤患者的OGM结果,与以前的细胞遗传学分析仅部分一致，有助于更好地定义克隆异质性，克服了由于细胞遗传学技术的细胞培养而导致的与克隆选择有关的偏见。在这两种情况下，OGM分析导致了分子标记的鉴定，帮助定义发病机制，分类，以及所分析患者的预后。尽管在研究血液病方面进行了广泛的努力，标准的细胞遗传学方法显示出无法超越的极限，而OGM是一种能够克服这些限制并以更高的分辨率提供细胞遗传学分析的工具。由于OGM在定义重复性区域方面也显示出局限性，将OGM与CBA组合以获得完整的细胞遗传学表征将是期望的。
