Figure 1. Genetic defects in 11 MDS patients.

(a) Number of acquired mutations in 11 patients with MDS, as determined by whole-exome sequencing at several time points (Supplementary Data 1) and confirmed by amplicon-based deep sequencing. In light grey, the number of mutations in genes previously implicated in the pathogenesis of myeloid malignancies are indicated (driver mutations)²,³,²⁵,⁴¹,⁴²,⁴³,⁴⁴, and in dark grey the number of mutations not previously implicated in myeloid malignancies (putative passenger mutations). (b) A positive correlation could be observed between age and the number of genetic defects (genetic and cytogenetic defects) at the time of first sampling. Pearson’s correlation coefficient (including a two-tailed P value calculated by Student’s t-test) was determined. (c) For each patient, all mutations in genes known to be recurrently mutated in myeloid malignancies are depicted as well as all cytogenetic defects detected by high-resolution SNP array and/or karyotype analysis. The colours match with the (sub)clones as depicted in Figs 2 and 3. *Indicates a mutated gene that is also affected by a copy number gain or loss or by a copy-neutral loss of heterozygosity (CN-LOH); ‘2’ indicates two different mutations affecting the same gene. (d) Distribution of the different types of alterations detected in the total set of patients. (e) Different types of single-nucleotide changes detected in all patients, with transitions in dark grey and transversions in light grey.