TP53 Abnormalities Are Underlying the Poor Outcome Associated with Chromothripsis in Chronic Lymphocytic Leukemia Patients with Complex Karyotype
Ramos-Campoy, Silvia (Institut Hospital del Mar d'Investigacions Mèdiques)
Puiggros, Anna (Institut Hospital del Mar d'Investigacions Mèdiques)
Kamaso, Joanna (Institut Hospital del Mar d'Investigacions Mèdiques)
Beà, Sílvia (Centro de Investigación Biomédica en Red de Cáncer)
Bougeon, Sandrine (Lausanne University Hospital)
Larráyoz, María José (Universidad Pública de Navarra)
Costa, Dolors (Centro de Investigación Biomédica en Red de Cáncer)
Parker, Helen (University of Southampton)
Rigolin, Gian Matteo (St. Anna University Hospital)
Blanco, María Laura (Institut d'Investigació Biomèdica Sant Pau)
Collado, Rosa (Consorcio Hospital General Universitario)
Ancín, Idoya (Hospital Universitario de Cruces (Barakaldo, País Basc))
Salgado, Rocío (Fundación Jiménez Díaz)
Moro-García, Marco A. (Hospital Universitario Central de Asturias)
Baumann, Tycho (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Gimeno, Eva (Institut Hospital del Mar d'Investigacions Mèdiques)
Moreno, Carol (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Salido, Marta (Institut Hospital del Mar d'Investigacions Mèdiques)
Calvo, Xavier (Institut Hospital del Mar d'Investigacions Mèdiques)
Calasanz, M.J (Universidad Pública de Navarra)
Cuneo, Antonio (Hematology Section. St. Anna University Hospital)
Nguyen-Khac, Florence (Sorbonne University)
Oscier, David (Royal Bournemouth Hospital)
Haferlach, Claudia (MLL Munich Leukemia Laboratory)
Strefford, Jonathan C (University of Southampton)
Schoumans, Jacqueline (Lausanne University Hospital)
Espinet, Blanca (Institut Hospital del Mar d'Investigacions Mèdiques)
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	TP53 ; Chromothripsis ; Chronic lymphocytic leukemia ; Genomic complexity ; Genomic microarrays ; Optical genome mapping
Publicado en:	Cancers, Vol. 14 Núm. 15 (august 2022) , p. 3715, ISSN 2072-6694

DOI: 10.3390/cancers14153715
PMID: 35954380

18 p, 4.4 MB

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