2026-04-29T19:35:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/83612024-11-29T17:28:31Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Cedena, M Teresa author Rapado, Inmaculada author Santos-Lozano, Alejandro author Ayala, Rosa author Onecha, Esther author Abaigar, María author Such, Esperanza author Ramos, Fernando author Cervera, José author Díez-Campelo, María author Sanz, Guillermo author Rivas, Jesús Hernández author Lucía, Alejandro author Martinez-Lopez, Joaquin author 2017-12-05 We evaluated the association of mutations in 34 candidate genes and response to azacitidine in 84 patients with myelodysplastic syndrome (MDS), with 217 somatic mutations identified by next-generation sequencing. Most patients (93%) had ≥1 mutation (mean=2.6/patient). The overall response rate to azacitidine was 42%. No clinical characteristic was associated with response to azacitidine. However, total number of mutations/patient was negatively associated with overall drug response (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.33-0.94; p=0.028), and a positive association was found for having ≥1 mutation in a DNA methylation-related gene: TET2, DNMT3A, IDH1 and/or IDH2 (OR: 4.76, 95%CI: 1.31-17.27; p=0.017). Mutations in TP53 (hazard ratio [HR]: 3.88; 95%CI: 1.94-7.75) and EZH2 (HR: 2.50; 95%CI: 1.23-5.09) were associated with shorter overall survival. Meta-analysis of 6 studies plus present data (n=815 patients) allowed assessment of the association of drug response with mutations in 9 candidate genes: ASXL1, CBL, EZH2, SF3B1, SRSF2, TET2, DNMT3A, IDH1/2 and TP53. TET2 mutations predicted a more favorable drug response compared with 'wild-type' peers (pooled OR: 1.67, 95%CI: 1.14-2.44; p=0.01). In conclusion, mutations in the DNA methylation pathway, especially TET2 mutations, and low number of total mutations are associated with a better response to azacitidine. Oncotarget. 2017 ;8(63):106948-106961. 10.18632/oncotarget.22157 1949-2553 1949-2553 Oncotarget 29291002 http://hdl.handle.net/20.500.12105/8361 Hypomethylating agents Mutational profile Myelodysplastic syndromes Next generation sequencing Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes