Hematology and Stem Cell Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari "Aldo Moro", 70124 Bari, Italy.
Section of Molecular Pathology, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari "Aldo Moro", 70124 Bari, Italy.
Genes (Basel). 2023 Dec 5;14(12):2180. doi: 10.3390/genes14122180.
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.
标准细胞遗传学技术（染色体带分析-CBA 和荧光原位杂交-FISH）在描述由两个或更多染色体断裂引起的复杂染色体重排和结构变体方面存在局限性。在这项研究中，我们应用光学基因组图谱（OGM）以高分辨率全面表征两种复杂的染色体重排。在病例 1 中，一名患有染色体碎裂的急性髓系白血病（AML）患者，OGM 分析与经典细胞遗传学技术完全一致，并有助于更好地细化染色体断裂点。病例 2 是一名非霍奇金淋巴瘤患者，其 OGM 结果与之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，克服了因细胞培养导致的细胞遗传学技术中克隆选择的偏倚。在这两种情况下，OGM 分析都导致了分子标记物的鉴定，有助于定义分析患者的发病机制、分类和预后。尽管为研究血液疾病做出了广泛的努力，但标准细胞遗传学方法仍存在不可逾越的局限性，而 OGM 是一种有能力克服这些局限性并提供更高分辨率细胞遗传学分析的工具。由于 OGM 在定义重复性质区域方面也存在局限性，因此将 OGM 与 CBA 相结合以获得完整的细胞遗传学特征将是理想的。
