Somatic mutations and CNVs in myelodysplastic syndromes

We analysed the mutational profile and copy number variation (CNV) of 34 genes related to myeloid pathologies in 106 patients diagnosed with myelodysplastic syndrome s using high-depth next generation sequencing. A total of 198 variants were identified in 94 patients (89%) and 85 patients (80%) had CNV abnormalities. Mutations in TP53, RUNX1, EZH2, KRAS, and U2AF1 had a negative impact on overall survival in univariate analyses (p<0.05). In the multivariate analysis including clinical variables, mutations in TP53 and EZH2 remained the only adverse prognostic factors for overall survival (hazard ratio [HR] 6.3 and 3.5, respectively). Considering these genes and two additional genes previou sly described to have prognostic value (ASXL1 and ETV6), we designed the "molecular prognostic score". The presence of a mutation in any of these genes decreased overall survival (p=0.001), even after adjusting for risk group (HR 2.7, 95% confidence interval 1.3-5.7). We found gains of copies in HRAS (41% of patients) and SF1 (34%), and loss of copies in ATRX (39%), GATA1 (34%), and TET2 (27%). Thus, high-sensitivity targeted sequencing found mutations or CNV in most of the patients, which is clinically relevant, even after adjusting for risk groups.