Clinical characteristics of patients with MAP2K1 or BRAF exon 12 mutations
| . | MAP2K1 mutated . | BRAF exon 12 mutated . | ||||
|---|---|---|---|---|---|---|
| MAP2K1 exon 2 . | MAP2K1 exon 3 . | All patients . | In-frame deletions . | In-frame insertions . | All patients . | |
| Patients, n | 36 | 18 | 54 | 27 | 12 | 39 |
| Age at diagnosis, y, median (range) | 2.7 (0.0-15.1) | 8.3 (1.7-17.1) | 4.8 (0.0-17.1) | 3.4 (0.2-17.9) | 6.2 (0.5-14.4) | 5.9 (0.2-17.9) |
| Age <3 y, n (%) | 19 (52.8) | 1 (5.6) | 20 (37.0) | 12 (44.4) | 3 (25.0) | 15 (38.5) |
| Age ≥3 y, n (%) | 17 (47.2) | 17 (94.4) | 34 (63.0) | 15 (55.6) | 9 (75.0) | 24 (61.5) |
| Sex, n (%) | ||||||
| Male | 23 (63.9) | 10 (55.6) | 33 (61.1) | 16 (59.3) | 5 (41.7) | 21 (53.8) |
| Female | 13 (36.1) | 8 (44.4) | 21 (38.9) | 11 (40.7) | 7 (58.3) | 18 (46.2) |
| Disease extent at diagnosis, n (%) | ||||||
| MS | 3 (8.3) | 1 (5.6) | 4 (7.4) | 7 (25.9) | 1 (8.3) | 8 (20.5) |
| SS | 33 (91.7) | 17 (94.4) | 50 (92.6) | 20 (74.1) | 11 (91.7) | 31 (79.5) |
| Detailed subtype, n (%) | ||||||
| MS-RO+ | 1 (2.8) | 0 (0.0) | 1 (1.9) | 3 (11.1) | 0 (0.0) | 3 (7.7) |
| MS-RO− | 2 (5.6) | 1 (5.6) | 3 (5.6) | 4 (14.8) | 1 (8.3) | 5 (12.8) |
| SS-bone | 30 (83.3) | 16 (88.9) | 46 (85.2) | 15 (55.6) | 11 (91.7) | 26 (66.7) |
| • SS-UFB | 22 (61.1) | 13 (72.2) | 35 (64.8) | 11 (40.7) | 8 (66.7) | 19 (48.7) |
| • SS-UFB, CNS-risk | 4 (11.1) | 1 (5.6) | 5 (9.3) | 4 (14.8) | 2 (16.7) | 6 (15.4) |
| • SS-MFB | 8 (22.2) | 3 (16.7) | 11 (20.4) | 4 (14.8) | 3 (25.0) | 7 (17.9) |
| SS-skin | 3 (8.3) | 0 (0.0) | 3 (5.6) | 2 (7.4) | 0 (0.0) | 2 (5.1) |
| SS-other | 0 (0.0) | 1 (5.6) | 1 (1.9) | 3 (11.1) | 0 (0.0) | 3 (7.7) |
| Disease site(s) at diagnosis, n (%) | ||||||
| Bone | 33 (91.7) | 17 (94.4) | 50 (92.6) | 20 (74.1) | 12 (100) | 32 (82.1) |
| • MFB lesions | 11 (30.6) | 3 (16.7) | 14 (25.9) | 7 (25.9) | 3 (25.0) | 10 (25.6) |
| • CNS-risk bone lesion(s) | 8 (22.2) | 1 (5.6) | 9 (16.7) | 8 (29.6) | 3 (25.0) | 11 (28.2) |
| • Spinal column lesion(s) | 6 (16.7) | 2 (11.1) | 8 (14.8) | 5 (18.5) | 2 (16.7) | 7 (17.9) |
| Skin | 5 (13.9) | 0 (0.0) | 5 (9.3) | 6 (22.2) | 0 (0.0) | 6 (15.4) |
| Liver | 0 (0.0) | 0 (0.0) | 0 (0.0) | 3 (11.1) | 0 (0.0) | 3 (7.7) |
| Hematopoietic system | 1 (2.8) | 0 (0.0) | 1 (1.9) | 1 (3.7) | 0 (0.0) | 1 (2.6) |
| Spleen | 0 (0.0) | 0 (0) | 0 (0.0) | 2 (7.4) | 0 (0.0) | 2 (5.1) |
| Lymph node | 2 (5.6) | 2 (11.1) | 4 (7.4) | 4 (14.8) | 1 (8.3) | 5 (12.8) |
| Lung | 1 (2.8) | 0 (0.0) | 1 (1.9) | 6 (22.2) | 0 (0.0) | 6 (15.4) |
| CNS | 1 (2.8) | 0 (0.0) | 1 (1.9) | 1 (3.7) | 0 (0.0) | 1 (2.6) |
| Follow-up, y, median (range) | 2.7 (0.2-15.2) | 4.3 (1.4-30.4) | 3.7 (0.2-30.4) | 6.3 (0.4-27.0) | 3.5 (0.7-9.4) | 5.3 (0.4-27.0) |
| Permanent consequences developed during follow-up, n (%) | ||||||
| DI | 1 (2.8) | 1 (5.6) | 2 (3.7) | 5 (18.5) | 0 (0.0) | 5 (12.8) |
| Death, n | 2 | 0 | 2 | 2 | 0 | 2 |
| . | MAP2K1 mutated . | BRAF exon 12 mutated . | ||||
|---|---|---|---|---|---|---|
| MAP2K1 exon 2 . | MAP2K1 exon 3 . | All patients . | In-frame deletions . | In-frame insertions . | All patients . | |
| Patients, n | 36 | 18 | 54 | 27 | 12 | 39 |
| Age at diagnosis, y, median (range) | 2.7 (0.0-15.1) | 8.3 (1.7-17.1) | 4.8 (0.0-17.1) | 3.4 (0.2-17.9) | 6.2 (0.5-14.4) | 5.9 (0.2-17.9) |
| Age <3 y, n (%) | 19 (52.8) | 1 (5.6) | 20 (37.0) | 12 (44.4) | 3 (25.0) | 15 (38.5) |
| Age ≥3 y, n (%) | 17 (47.2) | 17 (94.4) | 34 (63.0) | 15 (55.6) | 9 (75.0) | 24 (61.5) |
| Sex, n (%) | ||||||
| Male | 23 (63.9) | 10 (55.6) | 33 (61.1) | 16 (59.3) | 5 (41.7) | 21 (53.8) |
| Female | 13 (36.1) | 8 (44.4) | 21 (38.9) | 11 (40.7) | 7 (58.3) | 18 (46.2) |
| Disease extent at diagnosis, n (%) | ||||||
| MS | 3 (8.3) | 1 (5.6) | 4 (7.4) | 7 (25.9) | 1 (8.3) | 8 (20.5) |
| SS | 33 (91.7) | 17 (94.4) | 50 (92.6) | 20 (74.1) | 11 (91.7) | 31 (79.5) |
| Detailed subtype, n (%) | ||||||
| MS-RO+ | 1 (2.8) | 0 (0.0) | 1 (1.9) | 3 (11.1) | 0 (0.0) | 3 (7.7) |
| MS-RO− | 2 (5.6) | 1 (5.6) | 3 (5.6) | 4 (14.8) | 1 (8.3) | 5 (12.8) |
| SS-bone | 30 (83.3) | 16 (88.9) | 46 (85.2) | 15 (55.6) | 11 (91.7) | 26 (66.7) |
| • SS-UFB | 22 (61.1) | 13 (72.2) | 35 (64.8) | 11 (40.7) | 8 (66.7) | 19 (48.7) |
| • SS-UFB, CNS-risk | 4 (11.1) | 1 (5.6) | 5 (9.3) | 4 (14.8) | 2 (16.7) | 6 (15.4) |
| • SS-MFB | 8 (22.2) | 3 (16.7) | 11 (20.4) | 4 (14.8) | 3 (25.0) | 7 (17.9) |
| SS-skin | 3 (8.3) | 0 (0.0) | 3 (5.6) | 2 (7.4) | 0 (0.0) | 2 (5.1) |
| SS-other | 0 (0.0) | 1 (5.6) | 1 (1.9) | 3 (11.1) | 0 (0.0) | 3 (7.7) |
| Disease site(s) at diagnosis, n (%) | ||||||
| Bone | 33 (91.7) | 17 (94.4) | 50 (92.6) | 20 (74.1) | 12 (100) | 32 (82.1) |
| • MFB lesions | 11 (30.6) | 3 (16.7) | 14 (25.9) | 7 (25.9) | 3 (25.0) | 10 (25.6) |
| • CNS-risk bone lesion(s) | 8 (22.2) | 1 (5.6) | 9 (16.7) | 8 (29.6) | 3 (25.0) | 11 (28.2) |
| • Spinal column lesion(s) | 6 (16.7) | 2 (11.1) | 8 (14.8) | 5 (18.5) | 2 (16.7) | 7 (17.9) |
| Skin | 5 (13.9) | 0 (0.0) | 5 (9.3) | 6 (22.2) | 0 (0.0) | 6 (15.4) |
| Liver | 0 (0.0) | 0 (0.0) | 0 (0.0) | 3 (11.1) | 0 (0.0) | 3 (7.7) |
| Hematopoietic system | 1 (2.8) | 0 (0.0) | 1 (1.9) | 1 (3.7) | 0 (0.0) | 1 (2.6) |
| Spleen | 0 (0.0) | 0 (0) | 0 (0.0) | 2 (7.4) | 0 (0.0) | 2 (5.1) |
| Lymph node | 2 (5.6) | 2 (11.1) | 4 (7.4) | 4 (14.8) | 1 (8.3) | 5 (12.8) |
| Lung | 1 (2.8) | 0 (0.0) | 1 (1.9) | 6 (22.2) | 0 (0.0) | 6 (15.4) |
| CNS | 1 (2.8) | 0 (0.0) | 1 (1.9) | 1 (3.7) | 0 (0.0) | 1 (2.6) |
| Follow-up, y, median (range) | 2.7 (0.2-15.2) | 4.3 (1.4-30.4) | 3.7 (0.2-30.4) | 6.3 (0.4-27.0) | 3.5 (0.7-9.4) | 5.3 (0.4-27.0) |
| Permanent consequences developed during follow-up, n (%) | ||||||
| DI | 1 (2.8) | 1 (5.6) | 2 (3.7) | 5 (18.5) | 0 (0.0) | 5 (12.8) |
| Death, n | 2 | 0 | 2 | 2 | 0 | 2 |