Characterization of TP53 mutations not accompanied by 17p deletion
| Sample no. . | Mutation details . | CLL genetics . | Clonal expansion . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation (amino acid) . | Exon . | UPD (mutated allele > 50%) . | WAF1 . | Cytogenetics . | IGVH mutation status . | Initial clone size (mutated allele), % . | Clone size at CLL2H entry (mutated allele), % . | Clonal evolution/expansion . | Time interval (clonal evolution/expansion), mo . | Treatment during clonal evolution/expansion . | |
| 2H-27 | p.K132E | 5 | NA | 0.6 | 13q14− | UM | 0 | 25 | Yes | 10 | FC |
| 2H-38 | p.W146CfsX251 | 5 | No | 13q14− | M | NA | 5 | No* | 23 | Alemtuzumab | |
| 2H-92 | p.V173M | 5 | Yes | 10.5 | 13q14− | UM | 0 | 70 | Yes | 98 | DexaBeam, TBI/Cy + auto-SCT, FC, R-FC, CHOP |
| 2H-25 | p.R209KfsX6 | 6 | Yes | +12q13, 13q14− | UM | 75 | 90 | Yes | 5 | CHOP, FC | |
| P121 | p.R209KfsX6 | 6 | Yes | 13q14 bi | M | NA | 80 | NA | NA | ||
| 2H-60 | p.Y220C | 6 | Yes | 1.2 | Normal | UM | NA | 90 | NA | NA | |
| UL-86 | p.N239S | 7 | No | 14.9 | 13q14 bi | M | NA | 10 | Yes | 41 | Alemtuzumab† |
| 2H-41 | p.S241F | 7 | No | 0 | Normal | UM | 0 | 50 | Yes | 61 | FC |
| 2H-106 | p.C242W | 7 | No | 14.2 | 11q23− | UM | 0 | 5 | Yes | 54 | FC, DexaBeam, TBI/Cy + auto-SCT, FC |
| 2H-17 | p.L252SfsX93 | 7 | Yes | 6q21−, 13q14− | UM | NA | 100 | NA | NA | ||
| 2H-18 | p.R273L | 8 | Yes | 0.9 | 13q14 bi | M | NA | 70 | NA | NA | |
| 2H-76 | p.R290H | 8 | No | 67.3 | Normal | UM | 50 | 40 | No | 11 | FC |
| Sample no. . | Mutation details . | CLL genetics . | Clonal expansion . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation (amino acid) . | Exon . | UPD (mutated allele > 50%) . | WAF1 . | Cytogenetics . | IGVH mutation status . | Initial clone size (mutated allele), % . | Clone size at CLL2H entry (mutated allele), % . | Clonal evolution/expansion . | Time interval (clonal evolution/expansion), mo . | Treatment during clonal evolution/expansion . | |
| 2H-27 | p.K132E | 5 | NA | 0.6 | 13q14− | UM | 0 | 25 | Yes | 10 | FC |
| 2H-38 | p.W146CfsX251 | 5 | No | 13q14− | M | NA | 5 | No* | 23 | Alemtuzumab | |
| 2H-92 | p.V173M | 5 | Yes | 10.5 | 13q14− | UM | 0 | 70 | Yes | 98 | DexaBeam, TBI/Cy + auto-SCT, FC, R-FC, CHOP |
| 2H-25 | p.R209KfsX6 | 6 | Yes | +12q13, 13q14− | UM | 75 | 90 | Yes | 5 | CHOP, FC | |
| P121 | p.R209KfsX6 | 6 | Yes | 13q14 bi | M | NA | 80 | NA | NA | ||
| 2H-60 | p.Y220C | 6 | Yes | 1.2 | Normal | UM | NA | 90 | NA | NA | |
| UL-86 | p.N239S | 7 | No | 14.9 | 13q14 bi | M | NA | 10 | Yes | 41 | Alemtuzumab† |
| 2H-41 | p.S241F | 7 | No | 0 | Normal | UM | 0 | 50 | Yes | 61 | FC |
| 2H-106 | p.C242W | 7 | No | 14.2 | 11q23− | UM | 0 | 5 | Yes | 54 | FC, DexaBeam, TBI/Cy + auto-SCT, FC |
| 2H-17 | p.L252SfsX93 | 7 | Yes | 6q21−, 13q14− | UM | NA | 100 | NA | NA | ||
| 2H-18 | p.R273L | 8 | Yes | 0.9 | 13q14 bi | M | NA | 70 | NA | NA | |
| 2H-76 | p.R290H | 8 | No | 67.3 | Normal | UM | 50 | 40 | No | 11 | FC |
The table summarizes genetic background of CLL cases with TP53 mutation, types of TP53 mutations including the predicted residual activity of p53 toward transcriptional targets (WAF1), and details on clonal expansion. UPD was assessed by analyzing clone size of the wild-type and mutant allele. Mutant allele in excess of 50% was considered evidence for UPD. We also summarize the results of follow-up investigations to assess clonal expansion/evolution and treatment during this process.
TBI indicates total body irradiation; and SCT, stem cell transplantation.
Case 2H-38 showed disappearance of the mutation after treatment with alemtuzumab as confirmed by DHPLC and sequencing.
Case UL-86 showed clonal expansion after initial reduction in clone size after alemtuzumab therapy.