Figure 1.

Bar chart and Circos plot of the results of targeted NGS in 102 patients with MDS/MPN-U. (A) Bar diagram showing the frequencies of selected gene mutations in the cohort of patients (see the third paragraph of text for the 20 genes sequenced in all patients). The other 10 genes of interest were sequenced in fewer patients, as follows: CALR in 58 (57%), MPL in 73 (72%), CEBPA in 78 (76%), KRAS in 86 (84%), BRAF and CSF3R in 57 (56%) each, FLT3 and PTPN11 in 87 (85%) each, and MLL and STAG2 in 77 (75%) each. One patient each had >1 mutation in ASXL1, CBL, SETBP1, U2AF1, and ZRSR2; 2 patients each had >1 mutation in DNMT3A, NRAS, and SF3B1; 3 had >1 mutation in EZH2; 4 had >1 mutation in TP53, and 5 had >1 mutation in TET2. (B) Circos plot depicting the mutational frequencies of the 20 genes tested in all 102 patients (length of the arcs), along with the frequencies of cooccurrence of different mutations in the same patient (width of the ribbons). The strongest relationships of cooccurrence were seen between ASXL1 and SRSF2 (n = 10), ASXL1 and EZH2 (n = 9), SRSF2 and TET2 (n = 8), TET2 and JAK2 (n = 8), and ASXL1 and TET2 (n = 7). Other readily evident patterns of comutation included ASXL1 with RUNX1 (n = 6), TET2 with ZRSR2 (n = 6), JAK2 with ZRSR2 (n = 6), TET2 with DNMT3A (n = 5), TET2 with SF3B1 (n = 5), and TET2 with RUNX1 (n = 5). Mutations in the signaling genes JAK2, CBL, and NRAS were mostly mutually exclusive. Only 1 patient each had JAK2/CBL and JAK2/NRAS comutation. CBL or NRAS mutations did not cooccur with CALR or MPL mutations. All JAK2 mutations were V617F and all CSF3R mutations T618I. All SRSF2 and IDH2 mutations involved the P95 and R140 residues, respectively. Most NRAS mutations affected G12 or G13, most SF3B1 mutations affected K700 or K666, and most U2AF1 mutations affected the Q157 residue.