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Therapy-related myeloid neoplasms (t-MN) are frequently categorized according to previous therapy or pattern of cytogenetic abnormalities. Our objective was to evaluate and compare the mutational profile of  de novo  and t-MN by next generation sequencing. Sixty-four samples from patients with t-MN, previously treated for a solid tumor (mainly breast), or  de novo  AML, MDS, MDS/MPN were selected for our study. The library was prepared using diagnostic samples and the TruSight Myeloid sequencing panel targeting 54 genes. Samples were sequenced on a MiSeq. The classification system of the Belgian ComPerMed Expert Panel was used for the biological variant classification. Taking only pathogenic, probably pathogenic variants and variants of unknown significance into account 141 variants in 33 genes were found in 52 of 64 samples (81%; mean number of variants per patient = 2; range = [1–11]; 67 variants in 25 genes in t-MN and 74 variants in 25 genes in  de novo  MN). Overall, the most frequently detected variants included  TET2  (n = 22),  TP53  (n = 12),  DNMT3A  (n = 10) and  FLT3, NPM1, RUNX1  (n = 8 each). Our study revealed a high variety of variants both in t-MN and  de novo  MN patients. There was a higher incidence of  FLT3  and  TP53  variants in t-MN compared to  de novo  MN.

Next generation sequencing in therapy-related myeloid neoplasms compared to de novo myeloid neoplasms