Chromoanagenesis Detection in Chronic Lymphocytic Leukemia

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.