Table 4.
Frequency of mutations in genes involved in epigenetic regulatory mechanisms found to be recurrently altered in systemic mastocytosis.
| Gene | SM Diagnostic Subgroup | Mutated Cases/Total Cases (%) | Overall Frequency | WHO Subtype |
Mutated Cases/ Total Cases (%) |
Overall Frequency |
|
|---|---|---|---|---|---|---|---|
| ASXL1 | Non-AdvSM | 0/12 (0) [10] 6/309 (2) [12] 0/10 (0) [13] 0/44 (0) [29] 0/1 (0) [50] 0/26 (0) [68] 1/15 (7) [80] 0/6 (0) [85] 6/530 (1) [97] |
1% | BMM | 1/90 (1) [12] | 1% | |
| ISM | 0/10 (0) [10] 0/3 (0) [13] 0/1 (0) [50] 1/15 (7) [80] 6/530 (1) [97] |
4/211 (2) [12] 0/44 (0) [29] 0/26 (0) [68] 0/4 (0) [85] |
1% | ||||
| SSM | 0/2 (0) [10] 0/7 (0) [13] | 1/8 (13) [12] 0/2 (0) [85] |
5% | ||||
| AdvSM | 8/27 (30) [10] 2/13 (15) [12] 2/24 (8) [13] 25/106 (24) [29] 66/229 (29) [32] 12/25 (48) [50] 21/83 (25) [68] 2/10 (20) [80] 6/43 (14) [81] 5/13 (39) [85] 5/19 (26) [90] 35/210 (17) [97] |
24% | ASM | 0/1 (0) [10] 1/11 (9) [13] 0/2 (0) [50] 0/2 (0) [80] 1/6 (17) [90] |
1/9 (11) [12] 4/25 (16) [29] 0/3 (0) [68] 0/1 (0) [85] |
9% | |
| SM-AHN | 8/23 (35) [10] 1/13 (8) [13] 4/21 (19) [50] 6/43 (14) [81] 4/13 (31) [90] | 1/4 (25) [12] 21/80 (26) [29] 21/72 (29) [68] 5/12 (42) [85] |
25% | ||||
| MCL | 0/3 (0) [10] 0/2 (0) [50] |
0/1 (0) [29] 0/8 (0) [68] |
0% | ||||
| DNMT3A | Non-AdvSM | 14/309 (5) [12] 0/10 (0) [13] 2/44 (5) [29] 0/26 (0) [68] 2/15 (13) [80] 20/530 (4) [97] |
4% | BMM | 2/90 (2) [12] | 2% | |
| ISM | 10/211 (0.5) [12] 2/44 (5) [29] 2/15 (13) [80] | 0/3 (0) [13] 0/26 (0) [68] |
5% | ||||
| SSM | 2/8 (25) [12] | 0/7 (0) [13] | 13% | ||||
| AdvSM | 4/13 (31) [12] 3/24 (13) [13] 7/106 (7) [29] 1/83 (1) [68] 1/10 (10) [80] 2/19 (11) [90] 9/210 (4) [97] |
6% | ASM | 3/9 (33) [12] 0/25 (0) [29] 0/2 (0) [80] |
3/11 (27) [13] 0/3 (0) [68] 0/6 (0) [90] |
11% | |
| SM-AHN | 1/4 (25) [12] 7/80 (9) [29] 1/8 (13) [80] |
0/13 (0) [13] 1/72 (1) [68] 2/13 (15) [90] |
6% | ||||
| MCL | 0/1 (0) [29] | 0/8 (0) [68] | 0% | ||||
| EZH2 | Non-AdvSM | 0/12 (0) [10] 0/309 (0) [12] 1/10 (10) [13] 0/44 (0) [29] 0/26 (0) [68] 0/15 (0) [80] 0/6 (0) [85] |
0.2% | BMM | 0/90 (0) [12] | 0% | |
| ISM | 0/10 (0) [10] 0/3 (0) [13] 0/26 (0) [68] 0/4 (0) [85] |
0/211 (0) [12] 0/44 (0) [29] 0/15 (0) [80] |
0% | ||||
| SSM | 0/2 (0) [10] 1/7 (14) [13] | 0/8 (0) [12] 0/2 (0) [85] |
5% | ||||
| AdvSM | 2/27 (7) [10] 0/13 (0) [12] 4/24 (17) [13] 3/106 (3) [29] 17/305 (6) [32] 2/83 (2) [68] 0/10 (0) [80] 2/13 (15) [85] |
5% | ASM | 0/1 (0) [10] 2/11 (18) [13] 0/3 (0) [68] 0/1 (0) [85] |
0/9 (0) [12] 1/25 (4) [29] 0/2 (0) [80] |
6% | |
| SM-AHN | 2/23 (9) [10] 2/13 (15) [13] 2/72 (3) [68] 2/12 (17) [85] | 0/4 (0) [12] 2/80 (3) [29] 0/8 (0) [80] |
5% | ||||
| MCL | 0/3 (0) [10] 0/8 (0) [68] | 0/1 (0) [29] | 0% | ||||
| TET2 | Non-AdvSM | 0/12 (0) [10] 7/309 (2) [12] 0/10 (0) [13] 0/1 (0) [50] 2/29 (7) [51] 1/26 (4) [68] 1/15 (7) [80] 0/6 (0) [85] 2/13 (15) [88] |
3% | BMM | 2/90 (2) [12] | 2% | |
| ISM | 0/10 (0) [10] 0/3 (0) [13] 1/28 (4) [51] 1/15 (7) [80] 2/13 (15) [88] | 5/211 (2) [12] 0/1 (0) [50] 1/26 (4) [68] 0/4 (0) [85] |
3% | ||||
| SSM | 0/2 (0) [10] 0/7 (0) [13] 0/2 (0) [85] |
0/8 (0) [12] 1/1 (100) [51] |
5% | ||||
| AdvSM | 15/27 (56) [10] 2/13 (15) [12] 3/24 (13) [13] 137/329 (42) [32] 12/25 (48) [50] 12/35 (34) [51] 33/83 (40) [68] 5/10 (50) [80] 12/32 (38) [81] 6/13 (46) [85] 10/29 (35) [88] 5/19 (26) [90] |
39% | ASM | 0/1 (0) [10] 0/11 (0) [13] 3/9 (33) [51] 0/2 (0) [80] 2/5 (40) [88] |
1/9 (11) [12] 2/2 (100) [50] 0/3 (0) [68] 0/1 (0) [85] 1/6 (17) [90] |
21% | |
| SM-AHN | 15/23 (65) [10] 3/13 (23) [13] 9/23 (39) [51] 5/8 (63) [80] 6/12 (50) [85] 4/13 (31) [90] | 1/4 (25) [12] 9/21 (43) [50] 33/72 (46) [68] 12/32 (38) [81] 8/23 (35) [88] |
43% | ||||
| MCL | 0/3 (0) [10] 0/3 (0) [51] 0/1 (0) [88] | 1/2 (50) [50] 0/8 (0) [68] |
6% | ||||
Overall frequencies represent the weighted average of the percentage of patients with at least one mutation in that gene out of the total number of patients studied in the different cohorts for each SM subgroup. Abbreviations: AdvSM: advanced systemic mastocytosis (SM); ASM: aggressive SM; BMM: bone marrow mastocytosis; ISM: indolent SM; MCL: mast cell leukaemia; Non-AdvSM: non-advanced SM; SM-AHN: SM with an associated haematological neoplasm; SSM: smouldering SM.