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SUPPLEMENTARY DATA
Supplementary Tables
Supplementary Table 1. Detected variants in the whole cohort of CMML patients at diagnosis (n=56)
CMML
62
4
Gene
AEBP2
ASXL1
4
ASXL1
4
6
7
7
9
10
13
16
17
19
27
32
34
41
48
50
53
60
61
64
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
ASXL1
64
ASXL1
86
ASXL1
86
ASXL1
114
115
116
117
37
31
27
18
62
6
17
28
34
46
53
62
61
62
4
7
26
36
38
62
10
27
116
29
46
ASXL1
ASXL1
ASXL1
ASXL1
ATRX
BCOR
BRAF
CALR
CALR
CBL
CBL
CBL
CBL
CBL
CBL
CBL
CDH13
CDH13
CDH3
CREBBP
CREBBP
CREBBP
CREBBP
CREBBP
CSF3R
CSF3R
CSF3R
CTCF
CTCF
Variant
G>G/C
A>A/G
TCACCACTGCCATAGAGAGGCGGC>TCACC
ACTGCCATAGAGAGGCGGC/T
GA>GA/G
TC>TC/T
T>T/A
G>G/T
T>T/TA
C>C/T
G>G/T
A>A/AG
A>A/AG
C>C/T
A>A/AG
C>C/T
A>A/AG
C>C/T
A>A/AG
A>A/AG
CTG>CTG/C
A>A/AG
G>G/T
GA>GA/G
TCACCACTGCCATAGAGAGGCGGC>TCACC
ACTGCCATAGAGAGGCGGC/T
GA>GA/G
TCACCACTGCCATAGAGAGGCGGC>TCACC
ACTGCCATAGAGAGGCGGC/T
C>C/T
C>C/T
G>G/T
A>A/AG
A>A/G
G>G/A
T>T/C
A>A/G
A>A/G
G>G/A
T>T/C
G>G/A
G>G/T
G>G/A
G>G/C
G>G/A
C>C/G
G>G/A
C>C/T
G>G/A
T>T/C
G>G/A
C>C/CGCTGCT
C>C/G
C>C/T
C>C/T
C>C/G
G>G/A
G>G/A
Chr
12
20
Coordinate
19592744
31024260
Type
snv
snv
VAF(%)
14
49
20
31022402
deletion
6
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
31022416
31022898
31022615
31023821
31022613
31022592
31024662
31022441
31022441
31022589
31022441
31022851
31022441
31024758
31022441
31022441
31021542
31022441
31022697
31022416
deletion
deletion
snv
snv
insertion
snv
snv
insertion
insertion
snv
insertion
snv
insertion
snv
insertion
insertion
deletion
insertion
snv
deletion
9
45
28
56
46
52
37
35
43
43
37
46
42
49
38
43
43
34
47
12
20
31022402
deletion
6
20
31022416
deletion
12
20
31022402
deletion
6
20
20
20
20
X
X
7
19
19
11
11
11
11
11
11
11
16
16
16
16
16
16
16
16
1
1
1
16
16
31022592
31022637
31022487
31022441
76938584
39932591
140534599
13054612
13054612
119148922
119148919
119148991
119149003
119148991
119148967
119149251
83520115
83065791
68732113
3779482
3777826
3820773
3778302
3781195
36932047
36932047
36939403
67654676
67650711
snv
snv
snv
insertion
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
insertion
snv
snv
snv
snv
snv
snv
50
35
44
24
100
100
49
51
51
32
24
90
2
2
36
3
48
55
40
26
47
46
18
47
51
49
50
28
23
33
123
116
15
18
34
17
10
17
50
86
114
25
48
3
30
38
28
32
64
111
25
26
50
8
33
41
83
16
38
63
84
1
62
46
86
25
1
60
63
116
116
8
15
1
4
4
6
9
10
50
64
15
36
84
121
121
122
4
28
63
15
35
6
6
27
CTNNA1
CTNNA1
CUX1
DNMT3A
DNMT3A
DNMT3A
EP300
EZH2
EZH2
EZH2
EZH2
EZH2
FLT3
GATA1
GATA2
GCAT
IDH1
IDH2
IDH2
IDH2
IDH2
JAK2
JAK2
JAK2
JARID2
JARID2
KIT
KMT2A
KMT2D
KMT2D
KMT2D
KMT2D
KRAS
KRAS
LUC7L2
LUC7L2
MECOM
NF1
NF1
NF1
NF1
NF1
NPM1
NPM1
NRAS
NRAS
NRAS
NRAS
NRAS
NRAS
NRAS
NRAS
PDGFRA
PDGFRB
PHF6
PHF6
PHF6
PHLPP1
PTPN11
PTPN11
PTPN11
RAD21
RPS14
RUNX1
RUNX1
RUNX1
G>G/C
G>G/C
G>G/A
C>C/T
C>C/T
T>T/G
TCAG>TCAG/T
G>G/GCTTC
GT>GT/G
C>G/G
T>T/A
T>T/C
T>T/C
C>C/T
T>T/TG
C>C/T
G>G/A
C>C/T
C>C/T
C>C/T
C>C/T
G>G/T
G>G/T
G>G/T
G>G/A
A>A/G
A>A/T
G>G/A
G>G/T
C>C/T
G>G/A
C>C/A
C>C/A
C>C/T
A>A/C
A>A/C
C>C/A
T>T/C
T>T/C
G>G/A
G>G/A
G>G/T
C>C/CTCTG
C>C/CTCTG
C>C/T
A>A/C
C>C/T
T>T/TTAG
C>C/T
C>C/A
C>C/T
C>C/T
A>A/T
C>C/T
C>C/T
TG>TG/T
G>G/T
C>C/T
G>G/A
G>G/A
G>G/A
C>C/T
T>T/C
C>C/A
G>G/T
T>T/TCC
5
5
7
2
2
2
22
7
7
7
7
7
13
X
3
22
2
15
15
15
15
9
9
9
6
6
4
11
12
12
12
12
12
12
7
7
3
17
17
17
17
17
5
5
1
1
1
1
1
1
1
1
4
5
X
X
X
18
12
12
12
8
5
21
21
21
138266577
138269550
101891907
25457242
25466759
25523096
41574510
148544339
148515160
148525940
148507437
148506166
28608312
48649629
128205798
38211772
209113113
90631934
90631934
90631934
90631934
5073770
5073770
5073770
15497053
15496802
55599321
118374244
49426793
49433050
49433958
49426734
25398262
25398285
139107009
139107009
168861536
29557853
29557853
29562747
29548916
29586074
170837543
170837543
115258747
115256521
115258744
115258676
115258747
115256532
115258747
115258747
55127309
149512494
133551319
133511705
133511706
60646006
112926888
112926887
112926888
117878966
149823902
36231773
36252940
36252994
snv
snv
snv
snv
snv
snv
deletion
insertion
deletion
snv
snv
snv
snv
snv
insertion
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
insertion
insertion
snv
snv
snv
insertion
snv
snv
snv
snv
snv
snv
snv
deletion
snv
snv
snv
snv
snv
snv
snv
snv
snv
insertion
48
52
52
46
51
46
44
39
45
99
34
12
47
99
46
46
48
49
45
47
2
48
44
28
51
58
48
52
48
53
53
46
10
42
47
49
50
8
6
4
44
41
31
30
32
15
6
11
30
47
5
53
50
47
46
73
20
49
6
3
23
53
47
33
12
3
28
34
38
39
41
45
50
50
60
62
63
83
3
9
34
45
82
37
29
3
21
82
117
30
114
3
46
84
86
122
28
83
86
121
1
6
10
13
27
28
33
34
35
38
41
45
48
61
63
64
83
111
115
123
34
36
16
86
1
6
8
8
10
13
13
16
RUNX1
RUNX1
RUNX1
RUNX1
RUNX1
RUNX1
RUNX1
RUNX1
RUNX1
RUNX1
RUNX1
RUNX1
SETBP1
SETBP1
SETBP1
SETBP1
SETBP1
SF1
SF3A1
SF3B1
SF3B1
SF3B1
SF3B1
SFPQ
SFPQ
SH2B3
SH2B3
SH2B3
SH2B3
SH2B3
SMC1A
SMC1A
SMC1A
SMC3
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
SRSF2
STAG2
SUZ12
TERT
TERT
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
A>A/G
C>C/CG
C>C/T
A>A/G
G>G/A
G>G/A
AG>AG/A
T>T/C
C>C/T
A>A/G
A>A/G
G>G/A
C>C/T
A>A/G
G>G/A
G>G/C
C>C/T
AGGC>AGGC/A
C>C/A
T>T/C
T>T/C
T>T/C
T>T/G
G>G/A
A>A/G
G>G/A
G>G/A
G>G/A
G>G/C
C>C/T
C>C/T
C>C/T
T>T/C
A>A/C
G>G/T
G>G/T
G>G/T
G>G/A
G>G/C
G>G/C
G>G/C
G>G/T
G>G/GGGC
G>G/C
G>G/A
G>G/C
G>G/T
G>G/T
G>G/A
G>G/A
G>G/T
G>G/A
G>G/T
G>G/T
C>C/T
G>G/A
A>A/C
G>G/A
A>A/AT
C>C/T
CA>CA/C
G>G/A
C>C/T
TC>TC/T
CTT>CTT/C
AC>AC/A
21
21
21
21
21
21
21
21
21
21
21
21
18
18
18
18
18
11
22
2
2
2
2
1
1
12
12
12
12
12
X
X
X
10
17
17
17
17
17
17
17
17
17
17
17
17
17
17
17
17
17
17
17
17
X
17
5
5
4
4
4
4
4
4
4
4
36259324
36259256
36259171
36259324
36206725
36259184
36206765
36252886
36231792
36259324
36259324
36231786
42531184
42531908
42533267
42530117
42531184
64534502
30733688
198266834
198266834
198266834
198267360
35658085
35658319
111856640
111885287
111856607
111856571
111885484
53432008
53432008
53430710
112362759
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
74732959
123179197
30264461
1294186
1293767
106157402
106156729
106156480
106190855
106164778
106193979
106197177
106155513
snv
insertion
snv
snv
snv
snv
deletion
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
deletion
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
insertion
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
snv
insertion
snv
deletion
snv
snv
deletion
deletion
deletion
45
38
43
52
42
46
46
51
45
50
52
9
45
44
50
47
54
41
43
48
47
4
3
53
48
43
34
43
51
51
91
95
93
47
33
41
41
41
44
45
43
49
37
51
50
49
47
40
50
51
43
41
21
19
4
48
49
53
36
46
44
45
44
39
33
43
16
17
18
21
21
25
26
26
26
27
29
29
30
30
33
33
34
35
35
36
36
37
39
39
41
43
45
46
46
48
50
53
53
61
61
62
63
82
82
83
84
84
111
111
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
114
TET2
114
114
115
115
117
121
121
122
122
123
48
25
32
114
3
4
33
121
32
C>C/T
C>C/G
T>T/C
GAAAGGT>GAAAGGT/G
G>G/A
G>G/C
AAT>AAT/A
CTAT>CTAT/C
GC>GC/G
GATTGA>GATTGA/G
C>C/G
T>T/C
TC>TC/T
A>A/G
T>T/TA
C>C/A
C>C/CA
T>T/TGC
C>C/T
C>C/CT
C>C/CAG
AC>AC/A
T>T/TA
AG>AG/A
C>C/T
C>C/T
T>T/A
CT>CT/C
T>T/TA
AACTT>AACTT/A
TC>TC/T
C>C/G
A>A/G
G>G/GA
A>A/G
C>C/T
T>T/C
T>T/TG
G>G/GA
C>C/T
A>A/AT
T>T/G
GGC>GGC/G
G>G/A
TCCCCAGTGTTGAAACAGCA>TCCCCAGTG
TTGAAACAGCA/T
C>C/A
G>G/T
TC>TC/T
C>C/T
C>C/T
C>C/T
G>G/C
CT>CT/C
CT>CT/C
T>T/C
TG>TG/T
G>G/A
T>T/C
T>T/TCTCATA
A>A/G
G>G/A
G>G/C
G>G/A
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TET2
TIMM50
U2AF1
U2AF1
U2AF1
UMODL1
UMODL1
UMODL1
UMODL1
UMODL1,C
G>G/A
21orf128
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
106190860
106180792
106164767
106162582
106162586
106180838
106158479
106164071
106164076
106156791
106193794
106197285
106155748
106182914
106155673
106156862
106157873
106155729
106193748
106158442
106196261
106182952
106182970
106196772
106156072
106157845
106196829
106157205
106157794
106157177
106155920
106158275
106190861
106155340
106183004
106157074
106164758
106196492
106196718
106157002
106164929
106190851
106157960
106162495
snv
snv
snv
deletion
snv
snv
deletion
deletion
deletion
deletion
snv
snv
deletion
snv
insertion
snv
insertion
insertion
snv
insertion
insertion
deletion
insertion
deletion
snv
snv
snv
deletion
insertion
deletion
deletion
snv
snv
insertion
snv
snv
snv
insertion
insertion
snv
insertion
snv
deletion
snv
42
44
93
42
82
42
44
40
41
41
16
54
41
44
41
41
43
42
42
43
39
43
45
44
98
94
54
44
45
39
45
47
49
44
39
47
97
41
44
46
44
49
43
45
4
106157185
deletion
14
4
4
4
4
4
4
4
4
4
4
19
21
21
21
21
21
21
21
106197318
106197405
106155920
106157059
106156747
106157845
106180784
106190850
106197180
106197285
39971376
44524456
44514777
44514769
43539257
43531190
43543122
43491492
snv
snv
deletion
snv
snv
snv
snv
deletion
deletion
snv
deletion
snv
snv
insertion
snv
snv
snv
snv
10
23
35
38
31
38
42
41
41
85
38
43
43
13
46
50
52
48
21
43523985
snv
51
17
19
19
29
30
31
49
49
82
117
122
ZRSR2
ZRSR2
ZRSR2
ZRSR2
ZRSR2
ZRSR2
ZRSR2
ZRSR2
ZRSR2
ZRSR2
ZRSR2
G>G/A
G>G/C
C>C/CAGCCGG
C>C/T
C>C/T
GGA>GGA/G
G>G/C
C>C/CAGCCGG
G>G/A
AAGAG>AAGAG/A
C>C/T
X
X
X
X
X
X
X
X
X
X
X
15840875
15841228
15841230
15833879
15822297
15841008
15841228
15841230
15822321
15822271
15809121
chr: chromosome; VAF: variant allele frequency; snv: single nucleotide variant
snv
snv
insertion
snv
snv
deletion
snv
insertion
snv
deletion
snv
97
6
19
28
83
38
13
39
11
67
83
Supplementary Table 2. List of all the affected genes and frequency in the cohort of CMML patients in
samples at diagnosis (n=56).
Gene
Number of
patients
Cohort
frequency
Gene
Number of
patients
Cohort
frequency
TET2
40
71%
PHF6
2
4%
ASXL1
24
43%
SFPQ
2
4%
SRSF2
20
36%
TERT
2
4%
RUNX1
13
23%
MECOM
1
2%
ZRSR2
9
16%
ATRX
1
2%
CBL
7
13%
BCOR
1
2%
NRAS
7
13%
CDH3
1
2%
EZH2
5
9%
BRAF
1
2%
CREBBP
5
9%
CUX1
1
2%
UMODL1
5
9%
EP300
1
2%
SETBP1
5
9%
FLT3
1
2%
SH2B3
5
9%
GATA1
1
2%
NF1
4
7%
GCAT
1
2%
IDH2
4
7%
GATA2
1
2%
SF3B1
4
7%
IDH1
1
2%
KMT2D
4
7%
KIT
1
2%
CSF3R
3
5%
KMT2A
1
2%
JAK2
3
5%
PDGFRA
1
2%
PTPN11
3
5%
PDGFRB
1
2%
SMC1A
3
5%
PHLPP1
1
2%
U2AF1
3
5%
RAD21
1
2%
DNMT3A
3
5%
RPS14
1
2%
KRAS
2
4%
SF1
1
2%
CTNNA1
2
4%
SF3A1
1
2%
CDH13
2
4%
SMC3
1
2%
CTCF
2
4%
STAG2
1
2%
CALR
2
4%
SUZ12
1
2%
JARID2
2
4%
TIMM50
1
2%
LUC7L2
2
4%
AEBP2
1
2%
NPM1
2
4%
Supplementary Table 3. Patients with gene mutations in regions with copy number neutral loss of
heterozygosity (CNN-LOH).
Number of
patients
CNN-LOH region
Start
End
Size
4q13.3q35.2
4q13.3q35.2
4q13.3qter
4q13.3qter
11q13.3q25
11q13.2q25
11q13.2q25
7q22.1q36.3
17q25.3
12q21.2q24.33
7p12.3q21.11
10p12.1q21.1
13q14.11q31.3
14q11.2q21.3
70579280
89992346
111.229.207
108.964.973
65018466
67.393.850
70339930
98915957
78.966.914
75.863.034
45749533
29074038
43719771
20511672
190921709
190921709
79.692.502
81.956.736
134942626
134938470
134939692
159119220
81.041.938
133777902
77814597
57196819
93333822
50870199
120342429
100.929.363
190.921.709
190.921.709
69.924.160
67.544.620
64599762
60.203.263
2.075.024
57.914.868
32.065.064
28.122.781
49.614.051
30.358.527
4
3
1
1
1
1
1
1
1
Mutated gene
TET2
CBL
EZH2
SRSF2
KRAS
None of the
studied genes
Supplementary Table 4. Genes included in the 83 gene panel.
ABL1
Target region
Gene
(exon)
EED
4-9
AEBP2
full
EP300
full
KMT2A
full
SFPQ
full
ASXL1
9, 11, 12
ETV6
full
MLL2
full
SH2B3
full
ATRX
full
EZH2
full
MPL
10
SMC1A
full
BCOR
full
FLT3
14, 15, 20
NF1
full
SMC3
full
BCORL1
full
GATA1
2
NPM1
11, 12
SPARC
full
BRAF
full
GATA2
full
NRAS
1-3
SRSF2
1
CALR
9
GCAT
full
PDGFRA
full
STAG1
full
CBL
8, 9
GNAS
full
PDGFRB
full
STAG2
full
CBLB
9, 10
HRAS
2, 3
PHF6
full
SUZ12
full
CDH13
full
IDH1
4
PHLPP1
full
TERC
full
CDH3
full
IDH2
4
PTEN
5-8
TERT
full
CDKN2A
full
IKZF1
full
PTPN11
full
TET2
2-11
CEBPA
full
IRF1
full
RAD21
full
TGM2
full
CREBBP
full
JAK2
12-16
RPS14
full
TIMM50
full
CSF3R
full
Gene
Target region
Gene
(exon)
MECOM
full
Target region
Gene
(exon)
SF3B1
full
Target region
(exon)
10-16
JAK3
13
RUNX1
3-8
TP53
4-11
CSNK1A1 full
JARID2
full
SALL4
full
U2AF1
2, 6
CTCF
full
KDM6A
full
SBDS
full
UMODL1
full
CTNNA1
full
KIT
2,8-11,13,17 SETBP1
4
WT1
7, 9
CUX1
full
KRAS
1-3
SF1
full
ZRSR2
full
DNMT3A
full
LUC7L2
full
SF3A1
full
Supplementary Figures
Supplementary Figure Legends
Supplementary Figure 1. Number and type of mutations across the CMML patients at diagnosis.
(A) distribution of number of mutations detected per patient; (B) frequency of affected genes in the entire
cohort; (C) type of mutation; (D) mechanisms in which the main affected genes are involved.
Supplementary Figure 2. Prognostic impact of gene mutations. (A) OS and PFS curves according to
number of total mutations; (B) OS and PFS curves according to mutations in individual genes (ASXL1,
EZH2, NRAS, SRSF2 and TET2); (C) OS and PFS curves according to number of adverse risk gene
mutations (ASXL1, EZH2, NRAS, SRSF2); (D) OS and PFS curves according to combinations between
ASXL1 and TET2 mutations. See Table 3 for 3-year percentage overall survival and progression free
survival and confidence intervals. AR mutations: adverse risk gene mutations (ASXL1, EZH2, NRAS,
SRSF2). (E) OS and PFS curves according to combinations between TET2 mutations and adverse risk
genes (excluding ASXL1). See Table 3 for 3-year percentage overall survival and progression free
survival and confidence intervals. AR mutations excluding ASXL1 (EZH2, NRAS, SRSF2).
Supplementary Figure 1
A
B
C
D
Supplementary Figure 2
A
B
C
D
E