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UBE2A somatic variants in CML progression
presence of imatinib mesylate (1 μM final concentration) in com- bination with human recombinant GCSF (10 ng/mL) or IL3 (0.5 ng/mL).
At days 3 and 6, cells were analyzed using FACS for CD11b sur- face expression and imaged with confocal microscopy (Online Supplementary Methods).
Results
Single nucleotide variants acquired during chronic myeloid leukemia progression
Genomic DNA (gDNA) from matched CP/BC samples was obtained for each patient at diagnosis (CP) and after
Table 1. Single nucleotide variants and indels identified by exome sequencing in blast crisis samples and absent in the paired chronic phase control.
Patient
1
2
3
4
5
6 7
8
9
10
Disease progression
F Lymphoid
F Myeloid
M Myeloid
F Myeloid
F nd
M Lymphoid M Lymphoid
F Myeloid
F Lymphoid
F Myeloid
Time to BC from CP at diagnosis (months)
1
59
74
41
14
Gene Mutation
name ratio (aa substitution)
RTP2(A190V) 53% KCNH3(A314V) 59% FAT4(R1698W) 57%
FUT3(R354C) 48%
RUNX1(K194N) 68% SMARCA4(A945T) 55% UBE2A(D114V) 93% ABL1(F486S) 50% PTPN11(G503V) 41% AMER3(R709H) 41% LAMA2(P1025S) 49% GRIN3A(R1024*) 41% SMC5(L1102*) 27% MESDC2(E130del) 45% CCDC40(S17L) 34% NRAS(Q61R) 32% DEFB119(R42H) 46% IKZF1(N159S) 44% AK8(R125H) 67%
OncoScore39
10.22 5.61 57.19 30.21 73 48.69 25.66 85.8 41.25 34.16 10.79 5.95 24.13 28.07 8.89 81.65 0 72.76 18.39
8.58 0 5.54 18.97 12.28 15.77 81.02 77.48 76.11 46.29 25.66 85.8 83.5 3.32 20.44 70.25 0 47.33 16.1 28.17 85.8
52 - -
-
59
4
10
PPT1(V168A) 39% MDH1B(A272T) 47% GPR98(R1745C) 45%
CEL(E216Q) 46% LRP4(D449N) 54% CYP2B6(R145W) 40% BCR(F615W) 44% ASXL1(G641_fs) 37% EPB41L3(P963L) 37% FGFR4(V262M) 39% UBE2A(I33M) 39% ABL1(E255V) 28% BARD1(G527_fs) 28% BSN(R3264H) 26% EFCAB4B(V643M) 31% KRT7(R339W) 41% AP5M1(D289N) 38% XPO1(E571K) 32% HMCN1(S1371L) 53% ABCA13(T2019M) 53% ABL1(T315I) 45%
*Stop codon. OncoScore is a text-mining tool that scores genes according to their association with cancer based on available biomedical literature; higher scores corre- spond to a stronger association with cancer. BC: blast crisis; CP: chronic phase.
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