Genomic landscape of follicular lymphoma across a wide spectrum of clinical behaviors

While some follicular lymphoma (FL) patients do not require treatment or experience prolonged responses, others relapse early, and little is known about genetic alterations specific to patients with a particular clinical behavior. We selected 56 grade 1–3A FL patients according to their need of trea...

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Detalles Bibliográficos
Autores: Mozas, Pablo, López, Cristina, Grau, Marta, Nadeu, Ferran, Clot, Guillem, Valle, Sara, Kulis, Marta, Navarro, Alba, Ramis-Zaldivar, Joan Enric, González-Farré, Blanca, Rivas-Delgado, Alfredo, Rivero, Andrea, Frigola, Gerard, Balagué, Olga, Giné, Eva, Delgado, Julio, Villamor, Neus, Matutes, Estella, Magnano, Laura, García-Sanz, Ramón, Huet, Sarah, Russell, Robert B., Campo, Elías, López-Guillermo, Armando, Beà, Silvia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/347393
Acceso en línea:http://hdl.handle.net/10261/347393
https://api.elsevier.com/content/abstract/scopus_id/85151971078
Access Level:acceso abierto
Palabra clave:Copy number alteration
Follicular lymphoma
Genomics
Next‐generation sequencing
Prognosis
Survival
Descripción
Sumario:While some follicular lymphoma (FL) patients do not require treatment or experience prolonged responses, others relapse early, and little is known about genetic alterations specific to patients with a particular clinical behavior. We selected 56 grade 1–3A FL patients according to their need of treatment or timing of relapse: never treated (n = 7), non-relapsed (19), late relapse (14), early relapse or POD24 (11), and primary refractory (5). We analyzed 56 diagnostic and 12 paired relapse lymphoid tissue biopsies and performed copy number alteration (CNA) analysis and next generation sequencing (NGS). We identified six focal driver losses (1p36.32, 6p21.32, 6q14.1, 6q23.3, 9p21.3, 10q23.33) and 1p36.33 copy-neutral loss of heterozygosity (CN-LOH). By integrating CNA and NGS results, the most frequently altered genes/regions were KMT2D (79%), CREBBP (67%), TNFRSF14 (46%) and BCL2 (40%). Although we found that mutations in PIM1, FOXO1 and TMEM30A were associated with an adverse clinical behavior, definitive conclusions cannot be drawn, due to the small sample size. We identified common precursor cells harboring early oncogenic alterations of the KMT2D, CREBBP, TNFRSF14 and EP300 genes and 16p13.3-p13.2 CN-LOH. Finally, we established the functional consequences of mutations by means of protein modeling (CD79B, PLCG2, PIM1, MCL1 and IRF8). These data expand the knowledge on the genomics behind the heterogeneous FL population and, upon replication in larger cohorts, could contribute to risk stratification and the development of targeted therapies.

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