Chromothripsis represents a mechanism of massive chromosome shattering and reassembly leading to the formation of derivative chromosomes with abnormal functions and expression. It has been observed in many cancer types, importantly, including chronic lymphocytic leukemia (CLL). Due to the associated chromosomal rearrangements, it has a significant impact on the pathophysiology of the disease. Recent studies have suggested that chromothripsis may be more common than initially inferred, especially in CLL cases with adverse clinical outcome. Here, we review the main features of chromothripsis, the challenges of its assessment, and the potential benefit of its detection. We summarize recent findings of chromothripsis occurrence across hematological malignancies and address its causes and consequences in the context of CLL clinical features, as well as chromothripsis-related molecular abnormalities described in published CLL studies. Furthermore, we discuss the use of the current knowledge about genome functions associated with chromothripsis in the optimization of treatment strategies in CLL.

Center of Molecular Medicine Central European Institute of Technology Masaryk University Brno Czechia

Department of Internal Medicine Hematology and Oncology University Hospital Brno and Faculty of Medicine Masaryk University Brno Czechia

Institute of Medical Genetics and Genomics University Hospital Brno and Masaryk University Brno Czechia

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