TP53 Abnormalities Are Underlying the Poor Outcome Associated with Chromothripsis in Chronic Lymphocytic Leukemia Patients with Complex Karyotype.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_C9D031407863
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
TP53 Abnormalities Are Underlying the Poor Outcome Associated with Chromothripsis in Chronic Lymphocytic Leukemia Patients with Complex Karyotype.
Journal
Cancers
Author(s)
Ramos-Campoy S., Puiggros A., Kamaso J., Beà S., Bougeon S., Larráyoz M.J., Costa D., Parker H., Rigolin G.M., Blanco M.L., Collado R., Ancín I., Salgado R., Moro-García M.A., Baumann T., Gimeno E., Moreno C., Salido M., Calvo X., Calasanz M.J., Cuneo A., Nguyen-Khac F., Oscier D., Haferlach C., Strefford J.C., Schoumans J., Espinet B.
ISSN
2072-6694 (Print)
ISSN-L
2072-6694
Publication state
Published
Issued date
29/07/2022
Peer-reviewed
Oui
Volume
14
Number
15
Pages
3715
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes. Nine cth cases were analyzed using optical genome mapping (OGM). Patterns detected by genomic microarrays were compared and the prognostic value of cth was analyzed. Cth was distributed throughout the genome, with chromosomes 3, 6 and 13 being those most frequently affected. OGM detected 88.1% of the previously known copy number alterations and several additional cth-related rearrangements (median: 9, range: 3-26). Two patterns were identified: one with rearrangements clustered in the region with cth (3/9) and the other involving both chromothriptic and non-chromothriptic chromosomes (6/9). Cases with cth showed a shorter time to first treatment (TTFT) than non-cth patients (median TTFT: 2 m vs. 15 m; p = 0.013). However, when stratifying patients based on TP53 status, cth did not affect TTFT. Only TP53 maintained its significance in the multivariate analysis for TTFT, including cth and genome complexity defined by genomic microarrays (HR: 1.60; p = 0.029). Our findings suggest that TP53 abnormalities, rather than cth itself, underlie the poor prognosis observed in this subset.
Keywords
TP53, chromothripsis, chronic lymphocytic leukemia, genomic complexity, genomic microarrays, optical genome mapping
Pubmed
Web of science
Open Access
Yes
Create date
22/08/2022 13:54
Last modification date
23/01/2024 8:34
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