Characteristics of select CMG mutations
| CMG . | Function . | Mutation frequency . | Percent missense: disruptive* . | Percent occurring early in evolution† (no. early: no. late) . | Murine models . | ||
|---|---|---|---|---|---|---|---|
| FL, % . | DLBCL, % (GCB-like, %) . | BL, % . | |||||
| KMT2D | H3K4 methyltransferase | 72 | 24 (28) | 2 | 17:83 | 62 (43:26) | Knockout,49 knockdown50 |
| CREBBP | Lysine acetyltransferase | 65 | 11 (16) | 6 | 81:19 | 89 (42:5) | Knockout,56-58,60 knockdown61 |
| EZH2 | H3K27 methyltransferase | 25 | 6 (12) | 2 | 100:0 | 41 (9:13) | Point-mutation knock-in38,42 |
| EP300 | Lysine acetyltransferase | 15 | 6 (6) | 0 | 100:0 | 57 (8:6) | — |
| KMT2C | H3K4 methyltransferase | 13 | 5 (5) | 1 | 75:25 | 60 (3:2) | — |
| HIST1H1E | Linker histone | 14 | 17 (17) | 0 | 100:0 | 21 (3:11) | — |
| ARID1A | SWI/SNF component | 11 | 9 (10) | 7 | 0:100 | 31 (4:9) | — |
| SMARCA4 | SWI/SNF component | 1 | 8 (10) | 21 | ‡ | ‡ | — |
| CMG . | Function . | Mutation frequency . | Percent missense: disruptive* . | Percent occurring early in evolution† (no. early: no. late) . | Murine models . | ||
|---|---|---|---|---|---|---|---|
| FL, % . | DLBCL, % (GCB-like, %) . | BL, % . | |||||
| KMT2D | H3K4 methyltransferase | 72 | 24 (28) | 2 | 17:83 | 62 (43:26) | Knockout,49 knockdown50 |
| CREBBP | Lysine acetyltransferase | 65 | 11 (16) | 6 | 81:19 | 89 (42:5) | Knockout,56-58,60 knockdown61 |
| EZH2 | H3K27 methyltransferase | 25 | 6 (12) | 2 | 100:0 | 41 (9:13) | Point-mutation knock-in38,42 |
| EP300 | Lysine acetyltransferase | 15 | 6 (6) | 0 | 100:0 | 57 (8:6) | — |
| KMT2C | H3K4 methyltransferase | 13 | 5 (5) | 1 | 75:25 | 60 (3:2) | — |
| HIST1H1E | Linker histone | 14 | 17 (17) | 0 | 100:0 | 21 (3:11) | — |
| ARID1A | SWI/SNF component | 11 | 9 (10) | 7 | 0:100 | 31 (4:9) | — |
| SMARCA4 | SWI/SNF component | 1 | 8 (10) | 21 | ‡ | ‡ | — |
Missense mutations include single amino acid substitutions and coding indels. Disruptive mutations include premature stop codon and frameshift mutations. Data are from FL WES/WGS studies with available information19,24,25 and are represented as relative percentage.
The percent of mutations occurring early in evolution is calculated from studies of clonal ancestry across 65 patients with paired diagnosis and relapse biopsies.19,24-26 Early events are defined as those shared between all biopsies from the same patient. Late events are defined as those not present in all paired biopsies from the same patient.
Only 1 evaluable mutation (disruptive and clonal).