DNA damage response-related alterations define the genetic background of patients with chronic lymphocytic leukemia and chromosomal gains

[EN]The presence of chromosomal gains other than trisomy 12 suggesting a hyperdiploid karyotype is extremely rare in chronic lymphocytic leukemia (CLL) and is associated with a dismal prognosis. However, the genetic mechanisms and mutational background of these patients have not been fully explored....

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Detalles Bibliográficos
Autores: Hernández-Sánchez, María, Rodríguez-Vicente, Ana E., González Cascón y Marín, Isabel, Quijada Álamo, Miguel, Martín Izquierdo, Marta, Hernández Rivas, José Ángel, Benito Sánchez, Rocío, Hernández Rivas, Jesús María, Hernández Sánchez, Jesús María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/146012
Acceso en línea:http://hdl.handle.net/10366/146012
Access Level:acceso abierto
Palabra clave:DNA
Damage
Genetic
Patients
Leukemia
Chromosomal gains
Genes
Cytogenetic
Pathogenesis
Leukemia L1210
Leukemia, Lymphocytic, Chronic, B-Cell
3205.04 Hematología
leucemia linfocítica crónica de células B
leucemia L1210
Descripción
Sumario:[EN]The presence of chromosomal gains other than trisomy 12 suggesting a hyperdiploid karyotype is extremely rare in chronic lymphocytic leukemia (CLL) and is associated with a dismal prognosis. However, the genetic mechanisms and mutational background of these patients have not been fully explored. To improve our understanding of the genetic underpinnings of this subgroup of CLL, seven CLL patients with several chromosomal gains were sequenced using a next-generation sequencing (NGS)-targeted approach. The mutational status of 54 genes was evaluated using a custom-designed gene panel including recurrent mutated genes observed in CLL and widely associated with CLL pathogenesis. A total of 21 mutations were detected; TP53 (42.8%), ATM (28.5%), SF3B1 (28.5%), and BRAF (28.5%) were the most recurrently mutated genes. Of these mutations, 61.9% were detected in genes previously associated with a poor prognosis in CLL. Interestingly, five of the seven patients exhibited alterations in TP53 or ATM (deletion and/or mutation), genes involved in the DNA damage response (DDR), which could be related to a high genetic instability in this subgroup of patients. In conclusion, CLL patients with several chromosomal gains exhibit high genetic instability, with mutations in CLL driver genes and high-risk genetic alterations involving ATM and/or TP53 genes.

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