Clinical, biological, and prognostic implications of SF3B1 co-occurrence mutations in very low/low- and intermediate-risk MDS patients

[EN]SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurre...

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Detalles Bibliográficos
Autores: Janusz, Kamila, Izquierdo, Marta Martín, Cadenas, Félix López, Ramos, Fernando, Sánchez, Jesús María Hernández, Lumbreras, Eva, Robledo, Cristina, Del Real, Javier Sánchez, Caballero, Juan Carlos, Collado, Rosa, Bernal, Teresa, Pedro, Carme, Insunza, Andrés, de Paz, Raquel, Xicoy, Blanca, Salido, Eduardo, García, Joaquín Sánchez, Mínguez, Sandra Santos, García, Cristina Miguel, Muñoz, Ana María Simón, Sánchez Barba, Mercedes, Hernández Rivas, Jesús María, Abáigar ,María, Campelo, María Díez
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:dnet:gredos______::dc1bbdd08342289b19207fbf6f4d683d
Acceso en línea:http://hdl.handle.net/10366/171383
Access Level:acceso abierto
Palabra clave:Adult
Aged
Aged, 80 and over
DNA (Cytosine-5-)-Methyltransferases
DNA Methyltransferase 3A
DNA Mutational Analysis
DNA-Binding Proteins
Dioxygenases
Female
Humans
Male
Middle Aged
Mutation
Myelodysplastic Syndromes
Phosphoproteins
Prognosis
Proto-Oncogene Proteins
RNA Splicing Factors
fosfoproteínas
pronóstico
adulto
síndromes mielodisplásicos
humanos
mutación
anciano
análisis de mutaciones del ADN
proteínas de unión al ADN
mediana edad
dioxigenasas
proteínas protooncogénicas
Descripción
Sumario:[EN]SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurrent mutations on the outcome of MDS patients. In applying next-generation sequencing (NGS) with a 117 myeloid gene custom panel, we analyzed the co-occurrence of SF3B1 with other mutations to reveal their clinical, biological, and prognostic implications in very low/low- and intermediate-risk MDS patients. Mutations in addition to those of SF3B1 were present in 80.4% of patients (median of 2 additional mutations/patient, range 0-5). The most frequently mutated genes were as follows: TET2 (39.2%), DNMT3A (25.5%), SRSF2 (10.8%), CDH23 (5.9%), and ASXL1, CUX1, and KMT2D (4.9% each). The presence of at least two mutations concomitant with that of SF3B1 had an adverse impact on survival compared with those with the SF3B1 mutation and fewer than two additional mutations (median of 54 vs. 87 months, respectively: p = 0.007). The co-occurrence of SF3B1 mutations with specific genes is also linked to a dismal prognosis: SRSF2 mutations were associated with shorter overall survival (OS) than SRSF2wt (median, 27 vs. 75 months, respectively; p = 0.001), concomitant IDH2 mutations (median OS, 11 [mut] vs. 75 [wt] months; p = 0.001), BCOR mutations (median OS, 11 [mut] vs. 71 [wt] months; p = 0.036), and NUP98 and STAG2 mutations (median OS, 27 and 11 vs. 71 months, respectively; p = 0.008 and p = 0.002). Mutations in CHIP genes (TET2, DNMT3A) did not significantly affect the clinical features or outcome. Our results suggest that a more comprehensive NGS study in low-risk MDS SF3B1mut patients is essential for a better prognostic evaluation.

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