Ramos-Campoy Silvia, Kamaso Joanna, Puiggros Anna, Espinet Blanca
Translational Research on Hematological Neoplasms Group, Cancer Research Program, Hospital del Mar Research Institute, Barcelona, Spain.
Molecular Cytogenetics Laboratory, Pathology Department, Hospital del Mar, Barcelona, Spain.
Methods Mol Biol. 2025;2968:231-248. doi: 10.1007/978-1-0716-4750-9_13.
Chromoanagenesis events have been identified in chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries. Among the three events included within this term, chromothripsis is the most frequently reported. Its prevalence in CLL is low, ranging from 1 to 3% of patients in unselected cohorts, and it has been associated with poor prognostic factors, such as abnormal TP53 and genomic complexity, and dismal outcome. Published series of CLL cases with chromothripsis have been identified using sequencing technologies or genomic microarrays. Of note, chromosome banding analysis and fluorescence in situ hybridization, which are the most commonly applied techniques for the routine cytogenetic assessment of CLL patients, do not allow the detection of chromoanagenesis. Over the last years, optical genome mapping has been introduced, providing a more detailed description of these complex chromoanagenetic profiles including a thorough overview of the rearrangements involved. In this sense, OGM can detect the vast majority of copy number abnormalities related to chromothripsis but also several additional intra- and interchromosomal rearrangements involved in these complex events. This will probably allow the identification of more cases carrying chromoanagenesis events that would not be detected by conventional techniques. Notwithstanding, limited data are available regarding the underlying mechanisms and the clinical impact of chromothripsis, chromoanasynthesis, and chromoplexy in the development and evolution of CLL.
染色体骤变事件已在慢性淋巴细胞白血病（CLL）中被发现，CLL是西方国家最常见的白血病。在这个术语所包含的三种事件中，染色体碎裂是最常被报道的。它在CLL中的患病率较低，在未选择的队列中占患者的1%至3%，并且它与不良预后因素相关，如TP53异常和基因组复杂性，以及预后不良。已通过测序技术或基因组微阵列确定了已发表的伴有染色体碎裂的CLL病例系列。值得注意的是，染色体带型分析和荧光原位杂交是CLL患者常规细胞遗传学评估中最常用的技术，但它们无法检测到染色体骤变。在过去几年中，引入了光学基因组图谱，它能更详细地描述这些复杂的染色体骤变图谱，包括对所涉及重排的全面概述。从这个意义上说，OGM可以检测到与染色体碎裂相关的绝大多数拷贝数异常，还能检测到这些复杂事件中涉及的一些额外的染色体内和染色体间重排。这可能会使更多携带染色体骤变事件的病例被识别出来，而这些病例用传统技术是检测不到的。尽管如此，关于染色体碎裂、染色体融合和染色体混乱在CLL发生发展中的潜在机制和临床影响的数据仍然有限。
