TY - JOUR 
A1 - Cedena, María Teresa
AU - Rapado, María Inmaculada
AU - Santos-Lozano, Alejandro
AU - Ayala, Rosa
AU - Onecha, Esther
AU - Abaigar, María
AU - Such, Esperanza
AU - Ramos Ortega, Fernando
AU - Lucía Mulas, Alejandro
AU - Martínez López, Joaquín
T1 - Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes
Y1 - 2017
SN - 1949-2553
UR - http://hdl.handle.net/11268/7326
AB - 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.
KW - Myelodysplastic syndromes
KW - Genética
KW - Mutación
KW - Genética humana
LA - eng
ER -