Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Banco de datos
Tipo del documento
Revista
Intervalo de año de publicación
1.
Blood ; 128(11): 1490-502, 2016 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-27369867

RESUMEN

Angioimmunoblastic T-cell lymphoma (AITL) and other lymphomas derived from follicular T-helper cells (TFH) represent a large proportion of peripheral T-cell lymphomas (PTCLs) with poorly understood pathogenesis and unfavorable treatment results. We investigated a series of 85 patients with AITL (n = 72) or other TFH-derived PTCL (n = 13) by targeted deep sequencing of a gene panel enriched in T-cell receptor (TCR) signaling elements. RHOA mutations were identified in 51 of 85 cases (60%) consisting of the highly recurrent dominant negative G17V variant in most cases and a novel K18N in 3 cases, the latter showing activating properties in in vitro assays. Moreover, half of the patients carried virtually mutually exclusive mutations in other TCR-related genes, most frequently in PLCG1 (14.1%), CD28 (9.4%, exclusively in AITL), PI3K elements (7%), CTNNB1 (6%), and GTF2I (6%). Using in vitro assays in transfected cells, we demonstrated that 9 of 10 PLCG1 and 3 of 3 CARD11 variants induced MALT1 protease activity and increased transcription from NFAT or NF-κB response element reporters, respectively. Collectively, the vast majority of variants in TCR-related genes could be classified as gain-of-function. Accordingly, the samples with mutations in TCR-related genes other than RHOA had transcriptomic profiles enriched in signatures reflecting higher T-cell activation. Although no correlation with presenting clinical features nor significant impact on survival was observed, the presence of TCR-related mutations correlated with early disease progression. Thus, targeting of TCR-related events may hold promise for the treatment of TFH-derived lymphomas.


Asunto(s)
Genes Codificadores de los Receptores de Linfocitos T/genética , Linfadenopatía Inmunoblástica/genética , Linfoma Folicular/genética , Linfoma de Células T Periférico/genética , Mutación/genética , Transducción de Señal , Linfocitos T Colaboradores-Inductores/inmunología , Proteína de Unión al GTP rhoA/genética , Biomarcadores de Tumor/genética , Estudios de Cohortes , Estudios de Seguimiento , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Linfadenopatía Inmunoblástica/inmunología , Linfadenopatía Inmunoblástica/patología , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Linfoma de Células T Periférico/inmunología , Linfoma de Células T Periférico/patología , Estadificación de Neoplasias , Pronóstico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA