Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing

Myelodysplastic syndromes (MDS) are a group of myeloid hematological malignancies, with a high risk of progression to acute myeloid leukemia (AML). To explore the role of acquired mutations in MDS, 111 MDS-associated genes were screened using next-generation sequencing (NGS), in 125 patients. One or more mutations were detected in 84% of the patients. Some gene mutations are specific for MDS and were associated with disease subtypes, and the patterns of mutational pathways could be associated with progressive MDS. The patterns, frequencies and functional pathways of gene mutations are different, but somehow related, between MDS and AML. Multivariate analysis suggested that patients with ≥ 2 mutations had poor progression-free survival, while GATA1/GATA2, DNMT3A and KRAS/NRAS mutations were associated with poor overall survival. Based on a novel system combining IPSS-R and molecular markers, these MDS patients were further divided into 3 more accurate prognostic subgroups. A panel of 11 target genes was proposed for genetic profiling of MDS. The study offers new insights into the molecular signatures of MDS and the genetic consistency between MDS and AML. Furthermore, results indicate that MDS could be classified by mutation combinations to guide the administration of individualized therapeutic interventions.