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تسجيل

Genome Complexity in Chronic Lymphocytic Leukemia

المؤلف:  Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.

المصدر:  Hematology : Basic Principles and Practice

الجزء والصفحة:  8th E , P875

2026-09-21

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Array CGH and NGS studies have effectively clarified the level of genomic complexity in CLL and revealed that the average number of mutations in CLL cells at diagnosis lies between 10 and 20, which is one of the lowest among the adult cancers, confirming previous cytogenetic observations. The recent studies also revealed that no single unifying mutation is responsible for CLL. Array-based genomic profiling has extended previous cytogenetic data demonstrating that a subset of patients with CLL have complex genomic profiles pointing to the interplay between chromosomal abnormalities and somatic mutations that are associated with reduced OS. Moreover, telomere dysfunction in CLL and acute telomere attrition results in fusion events that contribute to genomic complexity such as chromothripsis, which is a high level of DNA damage that may occur during a single mitotic division Fig. 1. Chromothripsis has been shown to occur in approximately 5% of patients, primarily in patients with unmutated IGHV status (74%) and high-risk genomic aberrations (79%). The presence of chromothripsis and kataegis in CLL implies that multiple cancer genes can be disrupted in a single step, providing a “quantum leap” for the malignant potential of the initial CLL clone.

Fig1. CHROMOTHRIPSIS. (A) Conventional G-banded cytogenetic analysis showed a derivative chromosome 18 composed of additional chromosomal segments. (B) Various FISH probes confirmed that the derivative chromosome 18 is composed of segments of chromosome 5, 7, 18, and 22, whereby the fragments of multiple chromosomes are stitched together by paired end joining. (C) Array comparative genomic hybridization (aCGH) of chromosome 5 shows segments within both the p arm and q arm with gains (blue bars) and loss (red bars) of genomic DNA illustrating that there are frequent copy number changes in a localized region of a chromosome as a result of chromothripsis.