Mutations in LCH
| Patient no.* . | Age, y* . | Sex* . | Disease site* . | Stage* . | OncoMap† . | Pyrosequencing‡ . |
|---|---|---|---|---|---|---|
| Cohort I | ||||||
| 1 | 2 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (7.84%) |
| 2 | 6 | F | Bone | Unifocal | None | WT (0.00%) |
| 3 | NA | NA | Bone | NA | None | WT (1.32%) |
| 4 | 0.9 | F | Lymph node | Multifocal | BRAF V600E | BRAF V600E (15.35%) |
| 5 | 2 | M | Bone | Multifocal | BRAF V600E | BRAF V600E (11.39%) |
| 6 | 12 | M | Bone | Unifocal | None | WT (1.51%) |
| 7 | 7 | M | Bone | Unifocal | None | BRAF V600E (5.52%)‖ |
| 8 | 1.3 | M | Lymph node | Multifocal | BRAF V600E | BRAF V600E (25.56%) |
| 9 | 4 | M | Bone | Unifocal | BRAF V600E | NT |
| 10 | 5 | M | Soft tissue | Unifocal | BRAF V600E | BRAF V600E (20.09%) |
| 11 | 2 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (30.87%) |
| 12 | 1.6 | F | Bone | Multifocal | None | WT (0.00%) |
| 13 | 6 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (12.65%) |
| 14 | 1 | M | Bone | Unifocal | None | NT |
| 15 | 8 | M | Bone | Unifocal | None | WT (0.45%) |
| 16 | 9 | F | Bone | Unifocal | BRAF V600E | NT |
| 17 | 9 | M | Bone | Multifocal | None | NT |
| 18 | 17 | M | Bone | Unifocal | BRAF V600E, MET E168D | BRAF V600E (11.06%) |
| 19 | 11 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (18.73%) |
| 20 | 0.8 | F | Bone | Unifocal | BRAF V600E | BRAF V600E (29.91%) |
| 21 | 17 | M | Soft tissue | Unifocal | TP53 R175H | NT |
| 22 | 7 | F | Bone | Unifocal | BRAF V600E | BRAF V600E (4.87%) |
| 23 | 9 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (12.44%) |
| 24 | 2 | M | Bone | Unifocal | None | NT |
| 25 | 5 | F | Skin | Unifocal | BRAF V600E | BRAF V600E (8.94%) |
| 26 | 27 | M | Bone | Unifocal | CUBN I3189V | WT (0.55%) |
| 27 | 26 | M | Bone | NA | BRAF V600E | BRAF V600E (19.80%) |
| 28 | 43 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (26.31%) |
| 29 | 53 | M | Lung | Unifocal | None | NT |
| 30 | 25 | F | Thyroid | Unifocal | None | WT (2.01%) |
| 31 | 47 | F | Bone | Unifocal | None | WT (0.63%) |
| 32 | 31 | F | Bone | Multifocal | None§ | WT (0.45%) |
| 33 | 51 | F | Lung | Unifocal | None | NT |
| 34 | 48 | F | Thymus | Unifocal | None | NT |
| 35 | 35 | M | Bone | NA | Insufficient DNA | WT (0.26%) |
| Cohort II | ||||||
| 36 | 8 | M | Bone | NA | BRAF V600E | BRAF V600E (17.02%) |
| 37 | 40 | M | Bone | Unifocal | None | NT |
| 38 | 42 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (41.98%) |
| 39 | 51 | M | Lung | Unifocal | BRAF V600E | BRAF V600E (10.87%) |
| 40 | 54 | M | Lung | NA | None | WT (1.50%) |
| 41 | 10 | F | Soft tissue | Multifocal | None | WT (0.00%) |
| 42 | 11 | M | Bone | Unifocal | None | NT |
| 43 | 61 | M | Lung | Unifocal | None | WT (0.60%) |
| 44 | 24 | F | NA | Unifocal | Insufficient DNA | NT |
| 45 | 40 | M | Bone | Unifocal | None | WT (0.28%) |
| 46 | 48 | F | Lung | Unifocal | None | NT |
| 47 | 16 | M | Skin | Unifocal | Insufficient DNA | NT |
| 48 | 59 | F | Lung | Unifocal | BRAF V600E | BRAF V600E (10.54%) |
| 49 | 1.6 | F | Mediastinum | Unifocal | BRAF V600E | NT |
| 50 | 4 | F | Bone | Unifocal | BRAF V600E | BRAF V600E (25.79%) |
| 51 | 38 | F | Lung | Unifocal | None | WT (0.64%) |
| 52 | 1.3 | M | LN | Multifocal | BRAF V600E | BRAF V600E (27.49%) |
| 53 | 3 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (26.66%) |
| 54 | 59 | F | Lung | Unifocal | BRAF V600E | NT |
| 55 | 13 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (24.19%) |
| 56 | 56 | M | Lung | Unifocal | BRAF V600E | NT |
| 57 | 16 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (15.80%) |
| 58 | 20 | F | Soft tissue | Unifocal | BRAF V600E | NT |
| 59 | 12 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (35.57%) |
| 60 | 61 | M | Lung | Unifocal | BRAF V600E | BRAF V600E (12.91%) |
| 61 | 43 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (17.33%) |
| 62 | 51 | F | Lung | Unifocal | None | WT (1.94%) |
| Frozen | ||||||
| 63 | NA | NA | NA | NA | Not performed | BRAF V600E (9.17%) |
| Patient no.* . | Age, y* . | Sex* . | Disease site* . | Stage* . | OncoMap† . | Pyrosequencing‡ . |
|---|---|---|---|---|---|---|
| Cohort I | ||||||
| 1 | 2 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (7.84%) |
| 2 | 6 | F | Bone | Unifocal | None | WT (0.00%) |
| 3 | NA | NA | Bone | NA | None | WT (1.32%) |
| 4 | 0.9 | F | Lymph node | Multifocal | BRAF V600E | BRAF V600E (15.35%) |
| 5 | 2 | M | Bone | Multifocal | BRAF V600E | BRAF V600E (11.39%) |
| 6 | 12 | M | Bone | Unifocal | None | WT (1.51%) |
| 7 | 7 | M | Bone | Unifocal | None | BRAF V600E (5.52%)‖ |
| 8 | 1.3 | M | Lymph node | Multifocal | BRAF V600E | BRAF V600E (25.56%) |
| 9 | 4 | M | Bone | Unifocal | BRAF V600E | NT |
| 10 | 5 | M | Soft tissue | Unifocal | BRAF V600E | BRAF V600E (20.09%) |
| 11 | 2 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (30.87%) |
| 12 | 1.6 | F | Bone | Multifocal | None | WT (0.00%) |
| 13 | 6 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (12.65%) |
| 14 | 1 | M | Bone | Unifocal | None | NT |
| 15 | 8 | M | Bone | Unifocal | None | WT (0.45%) |
| 16 | 9 | F | Bone | Unifocal | BRAF V600E | NT |
| 17 | 9 | M | Bone | Multifocal | None | NT |
| 18 | 17 | M | Bone | Unifocal | BRAF V600E, MET E168D | BRAF V600E (11.06%) |
| 19 | 11 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (18.73%) |
| 20 | 0.8 | F | Bone | Unifocal | BRAF V600E | BRAF V600E (29.91%) |
| 21 | 17 | M | Soft tissue | Unifocal | TP53 R175H | NT |
| 22 | 7 | F | Bone | Unifocal | BRAF V600E | BRAF V600E (4.87%) |
| 23 | 9 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (12.44%) |
| 24 | 2 | M | Bone | Unifocal | None | NT |
| 25 | 5 | F | Skin | Unifocal | BRAF V600E | BRAF V600E (8.94%) |
| 26 | 27 | M | Bone | Unifocal | CUBN I3189V | WT (0.55%) |
| 27 | 26 | M | Bone | NA | BRAF V600E | BRAF V600E (19.80%) |
| 28 | 43 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (26.31%) |
| 29 | 53 | M | Lung | Unifocal | None | NT |
| 30 | 25 | F | Thyroid | Unifocal | None | WT (2.01%) |
| 31 | 47 | F | Bone | Unifocal | None | WT (0.63%) |
| 32 | 31 | F | Bone | Multifocal | None§ | WT (0.45%) |
| 33 | 51 | F | Lung | Unifocal | None | NT |
| 34 | 48 | F | Thymus | Unifocal | None | NT |
| 35 | 35 | M | Bone | NA | Insufficient DNA | WT (0.26%) |
| Cohort II | ||||||
| 36 | 8 | M | Bone | NA | BRAF V600E | BRAF V600E (17.02%) |
| 37 | 40 | M | Bone | Unifocal | None | NT |
| 38 | 42 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (41.98%) |
| 39 | 51 | M | Lung | Unifocal | BRAF V600E | BRAF V600E (10.87%) |
| 40 | 54 | M | Lung | NA | None | WT (1.50%) |
| 41 | 10 | F | Soft tissue | Multifocal | None | WT (0.00%) |
| 42 | 11 | M | Bone | Unifocal | None | NT |
| 43 | 61 | M | Lung | Unifocal | None | WT (0.60%) |
| 44 | 24 | F | NA | Unifocal | Insufficient DNA | NT |
| 45 | 40 | M | Bone | Unifocal | None | WT (0.28%) |
| 46 | 48 | F | Lung | Unifocal | None | NT |
| 47 | 16 | M | Skin | Unifocal | Insufficient DNA | NT |
| 48 | 59 | F | Lung | Unifocal | BRAF V600E | BRAF V600E (10.54%) |
| 49 | 1.6 | F | Mediastinum | Unifocal | BRAF V600E | NT |
| 50 | 4 | F | Bone | Unifocal | BRAF V600E | BRAF V600E (25.79%) |
| 51 | 38 | F | Lung | Unifocal | None | WT (0.64%) |
| 52 | 1.3 | M | LN | Multifocal | BRAF V600E | BRAF V600E (27.49%) |
| 53 | 3 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (26.66%) |
| 54 | 59 | F | Lung | Unifocal | BRAF V600E | NT |
| 55 | 13 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (24.19%) |
| 56 | 56 | M | Lung | Unifocal | BRAF V600E | NT |
| 57 | 16 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (15.80%) |
| 58 | 20 | F | Soft tissue | Unifocal | BRAF V600E | NT |
| 59 | 12 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (35.57%) |
| 60 | 61 | M | Lung | Unifocal | BRAF V600E | BRAF V600E (12.91%) |
| 61 | 43 | M | Bone | Unifocal | BRAF V600E | BRAF V600E (17.33%) |
| 62 | 51 | F | Lung | Unifocal | None | WT (1.94%) |
| Frozen | ||||||
| 63 | NA | NA | NA | NA | Not performed | BRAF V600E (9.17%) |
NT indicates not tested (because of insufficient DNA for analysis); NA, not applicable; BRAF, B-Raf; MET, c-met proto-oncogene; TP53, p53 tumor suppressor gene; KRAS, K-Ras; CUBN, cubilin (intrinsic factor-cobalamin receptor); and None, none of the 983 mutant alleles measured by OncoMap was detected or was validated after detection during initial iPLEX screening.
Cohort I and Cohort II are composed of separately retrieved batches of archived patient material. Frozen indicates a fresh frozen LCH sample for which no clinical information was available.
Validated mutations identified by OncoMap mass spectrometric genotyping. Amino acid changes produced by specific mutations are indicated using standard designations.
BRAF allele status based on mutant allele abundance determined by pyrosequencing. The percentage of mutant alleles detected in each sample is shown in parentheses. BRAF V600E status was called on samples in which mutant sequences represented > 4% of total BRAF sequences (“Methods”).
Sample failed genotyping on hME analysis, but no mutations were detected on iPLEX analysis.
Because the pyrosequencing test is a clinically validated test performed in a Clinical Laboratory Improvement Amendment-certified laboratory, sample number 7 was assigned mutant BRAF V600E status.