Table 2.
Characteristics of HER2 mutations in patients stratified according to the HER2 amplification status.
| Characteristics | No. of cases (%) | P | ||
|---|---|---|---|---|
| Total (n = 529a) | HER2 amplification-positive (n = 477) | HER2 amplification-negative (n = 52) | ||
| ERBB2 exon | ||||
| 19 | 31 (5.9) | 17 (3.6) | 14 (26.9) | <0.001 |
| 20 | 38 (7.2) | 28 (5.9) | 10 (19.2) | |
| 21 | 27 (5.1) | 25 (5.2) | 2 (3.8) | |
| Other | 433 (81.9) | 407 (85.3) | 26 (50.0) | |
| Mutation site | ||||
| ECD | 225 (42.5) | 212 (44.4) | 13 (25.0) | <0.001 |
| TKI | 153 (28.9) | 123 (25.8) | 30 (57.7) | |
| Other | 151 (28.5) | 142 (29.8) | 9 (17.3) | |
| Variant classification | ||||
| Missense | 488 (92.2) | 443 (92.9) | 45 (86.5) | <0.001 |
| Nonsense | 19 (3.6) | 19 (4.0) | 0 (0.0) | |
| Frame shift | 15 (2.8) | 8 (1.7) | 7 (13.5) | |
| Other | 7 (1.3) | 7 (1.5) | 0 (0.0) | |
| Variant type | ||||
| SNP | 514 (97.2) | 469 (98.3) | 45 (86.5) | <0.001 |
| INS | 6 (1.1) | 2 (0.4) | 4 (7.7) | |
| DEL | 9 (1.7) | 6 (1.3) | 3 (5.8) | |
| VAF mean ± SD | 2.1 ± 9.0 | 1.2 ± 7.0 | 10.2 ± 17.4 | <0.001 |
| Clonality status | ||||
| Clonal | 24 (4.5) | 15 (3.1) | 9 (17.3) | <0.001 |
| Subclonal | 505 (95.5) | 462 (96.9) | 43 (82.7) | |
| Hotspot mutations | ||||
| p.V777L | 13 (2.5) | 9 (1.9) | 4 (7.7) | <0.001 |
| p.D769Y/H | 11 (2.1) | 4 (0.8) | 7 (13.5) | |
| p.L755S | 10 (1.9) | 7 (1.5) | 3 (5.8) | |
| p.S310F/Y | 9 (1.7) | 4 (0.8) | 5 (9.6) | |
| Other | 486 (91.9) | 453 (95.0) | 33 (63.5) | |
DEL deletion mutation, ECD extracellular domain, HER2 human epidermal growth factor receptor 2, INS insertion mutation, SNP single-nucleotide polymorphism, TKI tyrosine kinase domain, VAF variant allele frequency.
aStatistical analysis based on the mutation number.