Analysis of concomitant genetic aberrations in AML with somatic TP53 mutations
| No. . | TP53 VAF, % . | TP53 and concomitant mutations . | No. of mutated colonies (%) . | Copy number alterations . | ||||
|---|---|---|---|---|---|---|---|---|
| Losses . | Gains . | |||||||
| No. . | Length, bp . | No. . | Length, bp . | . | ||||
| 7549 | 65.9 | TP53: p.E221Gfs*26 | 44 of 60 (73) | 28 | 285.789.803 | 34 | 32.999.479 | |
| SRSF2: p.P95L | 38 of 60 (63) | |||||||
| BCL11A: p.P702L | 26 of 60 (43) | |||||||
| 5266 | 44.0 | TP53: p.L195P | 10 of 11 (91) | 80 | 402.787.349 | 21 | 9.619.914 | |
| ATP1A1: p.N483S | 6 of 11 (55) | |||||||
| TP53: p.Q165* | 5 of 11 (45) | |||||||
| 5273 | 52.0 | TP53: p.M237I | 107 of 112 (96) | 36 | 572.663.152 | 34 | 58.851.203 | |
| TP53: p.P152L | 106 of 112 (95) | |||||||
| 7317 | 88.1 | TP53: p.Asp228* | 18 of 18 (100) | 52 | 367.103.483 | 45 | 87.828.354 | |
| 7509 | 64.0 | TP53: p.V157F | 67 of 67 (100) | 38 | 182.926.187 | 30 | 55.245.921 | |
| DNMT3A: p.Q886R | 67 of 67 (100) | |||||||
| 7071 | 54.4 | TP53: p.R196P | 62 of 62 (100) | 27 | 131.583.940 | 113 | 316.102.979 | |
| TP53: p.K132* | 60 of 62 (97) | |||||||
| FLT3: p.D835H | 57 of 62 (92) | |||||||
| PTPN11: p.D61Y | 2 of 62 (3) | |||||||
| 5652 | 89.9 | TP53: p.R175H | 38 of 38 (100) | NA | NA | NA | NA | |
| ASXL1: p.G658* | 37 of 38 (97) | |||||||
| IDH2: p.R140Q | 20 of 38 (53) | |||||||
| RUNX1: p.V179C fs* 34 | 19 of 38 (50) | |||||||
| 7139 | 51.9 | TP53: p.I255N | 55 of 55 (100) | NA | NA | NA | NA | |
| No. . | TP53 VAF, % . | TP53 and concomitant mutations . | No. of mutated colonies (%) . | Copy number alterations . | ||||
|---|---|---|---|---|---|---|---|---|
| Losses . | Gains . | |||||||
| No. . | Length, bp . | No. . | Length, bp . | . | ||||
| 7549 | 65.9 | TP53: p.E221Gfs*26 | 44 of 60 (73) | 28 | 285.789.803 | 34 | 32.999.479 | |
| SRSF2: p.P95L | 38 of 60 (63) | |||||||
| BCL11A: p.P702L | 26 of 60 (43) | |||||||
| 5266 | 44.0 | TP53: p.L195P | 10 of 11 (91) | 80 | 402.787.349 | 21 | 9.619.914 | |
| ATP1A1: p.N483S | 6 of 11 (55) | |||||||
| TP53: p.Q165* | 5 of 11 (45) | |||||||
| 5273 | 52.0 | TP53: p.M237I | 107 of 112 (96) | 36 | 572.663.152 | 34 | 58.851.203 | |
| TP53: p.P152L | 106 of 112 (95) | |||||||
| 7317 | 88.1 | TP53: p.Asp228* | 18 of 18 (100) | 52 | 367.103.483 | 45 | 87.828.354 | |
| 7509 | 64.0 | TP53: p.V157F | 67 of 67 (100) | 38 | 182.926.187 | 30 | 55.245.921 | |
| DNMT3A: p.Q886R | 67 of 67 (100) | |||||||
| 7071 | 54.4 | TP53: p.R196P | 62 of 62 (100) | 27 | 131.583.940 | 113 | 316.102.979 | |
| TP53: p.K132* | 60 of 62 (97) | |||||||
| FLT3: p.D835H | 57 of 62 (92) | |||||||
| PTPN11: p.D61Y | 2 of 62 (3) | |||||||
| 5652 | 89.9 | TP53: p.R175H | 38 of 38 (100) | NA | NA | NA | NA | |
| ASXL1: p.G658* | 37 of 38 (97) | |||||||
| IDH2: p.R140Q | 20 of 38 (53) | |||||||
| RUNX1: p.V179C fs* 34 | 19 of 38 (50) | |||||||
| 7139 | 51.9 | TP53: p.I255N | 55 of 55 (100) | NA | NA | NA | NA | |
Concomitant mutations were initially determined by whole-exome sequencing and targeted deep sequencing (samples 5652 and 7139), respectively, of bulk leukemia cells and then assessed in CFU-GM colonies derived from sorted Lin-CD34+/CD38−/CD99− single cells. A total of 423 colonies were assessed, with a median of 58.5 colonies per samples (range, 11-112). Copy-number alterations were assessed by whole-exome sequencing of bulk leukemia cells. The length of gains and losses refers to the total number of alterations observed per sample.
NA, not available; VAF, variant allele frequency of TP53 as determined by targeted deep sequencing of diagnostic specimens.