BTK mutations identified via whole-exome sequencing and digital droplet polymerase chain reaction in patients with CLL after relapse with tirabrutinib
| Patient . | BTK amino acid change . | WT codon . | Mutant codon . | CCF from WES (%) . | VAF from ddPCR (%) . |
|---|---|---|---|---|---|
| CLL-1 | L528W | TTG | TGG | 86.8 | 78.6 |
| CLL-2 | C481S | TGC | TCC | Not called | 16.4 |
| CLL-3 | None detected | ||||
| CLL-4 | C481S | TGC | TCC | 22.4 | 34.5 |
| T474I | ACT | ATT | 50.4 | 62.4 | |
| CLL-5 | L528W | TTG | TGG | 91.0 | 79.3 |
| CLL-6 | C481S | TGC | TCC | Not detected | 1.9 |
| L528W | TTG | TGG | Not detected | 0.71 | |
| T474I | ACT | ATT | 34.4 | 12 | |
| E108K | GAA | AAA | 56.9 | Not tested | |
| CLL-7 | None detected | ||||
| CLL-8 | C481S | TGC | TCC | Not called | 17.9 |
| C481S | TGC | ACG | Not called | 5.3 | |
| L528W | TTG | TGG | Not detected | 0.16 | |
| T474I | ACT | ATT | 5.0 | 5.8 | |
| CLL-9 | None detected | ||||
| Patient . | BTK amino acid change . | WT codon . | Mutant codon . | CCF from WES (%) . | VAF from ddPCR (%) . |
|---|---|---|---|---|---|
| CLL-1 | L528W | TTG | TGG | 86.8 | 78.6 |
| CLL-2 | C481S | TGC | TCC | Not called | 16.4 |
| CLL-3 | None detected | ||||
| CLL-4 | C481S | TGC | TCC | 22.4 | 34.5 |
| T474I | ACT | ATT | 50.4 | 62.4 | |
| CLL-5 | L528W | TTG | TGG | 91.0 | 79.3 |
| CLL-6 | C481S | TGC | TCC | Not detected | 1.9 |
| L528W | TTG | TGG | Not detected | 0.71 | |
| T474I | ACT | ATT | 34.4 | 12 | |
| E108K | GAA | AAA | 56.9 | Not tested | |
| CLL-7 | None detected | ||||
| CLL-8 | C481S | TGC | TCC | Not called | 17.9 |
| C481S | TGC | ACG | Not called | 5.3 | |
| L528W | TTG | TGG | Not detected | 0.16 | |
| T474I | ACT | ATT | 5.0 | 5.8 | |
| CLL-9 | None detected | ||||
CCF calculated from WES and VAFs from ddPCR are included.
“Not detected” denotes mutations that were not called with our WES variant caller and were not visualized by eye in the raw sequencing read data.
“Not called” denotes mutations that were not detected with our WES variant caller but were visualized by eye on raw sequencing reads, likely because of low-confidence variant calling of low VAF mutations within low-coverage data.
CCF, cancer cell fraction; ddPCR, digital droplet polymerase chain reaction; VAF, variant allele frequency; WES, whole-exome sequencing; WT, wild-type.