Table 3.
Patient Molecular Disease Characteristics and Response
| Patient | Sex | Age (years) | Melanoma Type | M Stage | KIT Mutation | PCR Copy Number* | FISH Copy Number† | Months of Treatment | Best Response | Time to Progression (months) | Survival (months) | Survival Status | Sequenom |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Female | 79 | Mucosal | M1c | Exon 11 insertion PYD577-582 | N/T | N/T | 6 | PR | 4.7 | 12.9 | Dead | |
| 2 | Female | 61 | Mucosal | M1c | Exon 17 D820Y | 12.25 | 1.5 | 10 | PR | 10.2 | 19.3 | Dead | |
| 3 | Female | 69 | Acral-lentiginous | M1b | 5.96 | 1.3 | 1 | PD | 7.4 | 8.8 | Dead | ||
| 4 | Male | 57 | Chronically sun-damaged | M1c | 16.59 | 1.8 | 3 | PD | 5.0 | 11.5 | Dead | ||
| 5 | Female | 62 | Mucosal | M1c | 7.58 | N/T | 2 | PD | 2.6 | 11.9 | Dead | ||
| 6 | Male | 56 | Acral-lentiginous | M1b | 6.19 | 2.4 | 2 | PD | 3.5 | 4.5 | Dead | ||
| 7 | Male | 69 | Mucosal | M1c | 12.75 | N/T | 4 | PD | 5.8 | 16.2 | Dead | ||
| 8 | Female | 81 | Mucosal | M1c | 7.94 | N/T | 1 | PD | 1.0 | 3.8 | Alive | NRAS G12C | |
| 9 | Female | 72 | Mucosal | M1a | 5.76 | 1.5 | 2 | PD | 1.3 | 9.8 | Dead | ||
| 10 | Female | 55 | Mucosal | M1b | 7.02 | 4.1 | 11 | SD | 10.6 | 18.3 | Dead | ||
| 11 | Female | 59 | Acral-lentiginous | M1c | 6.33 | 2.3 | 1 | PD | 0.9 | 2.8 | Dead | NRAS Q61K | |
| 12 | Female | 59 | Mucosal | M1b | Exon 11 L576P | 11.22 | N/T | 11 | PR | 27.1 | 27.1 | Alive | |
| 13 | Female | 75 | Mucosal | M1b | 5.37 | N/T | 3 | SD | 5.6 | 12.5 | Dead | ||
| 14 | Female | 47 | Mucosal | M1c | Exon 11 L576P | 14.22 | 6.8 | 3 | PR | 2.6 | 7.3 | Dead | |
| 15 | Male | 84 | Acral-lentiginous | M1c | 7.06 | 1 | 2 | PD | 1.6 | 21.8 | Dead | ||
| 16‡ | Female | 53 | Acral-lentiginous | M1b | Exon 11 deletion WKVVE557-560 | N/T | N/T | 11 | SD | 10.6 | 24.3 | Dead | |
| 17 | Female | 75 | Mucosal | M1b | Exon 11 W557R | 2.64 | 1.4 | 3 | PD | 3.9 | 4.8 | Dead | |
| 18 | Male | 52 | Mucosal | M1c | Exon 11 V559A | 4.31 | N/T | 2 | PD | 1.5 | 18.0 | Dead | NRAS Q61H |
| 19 | Male | 66 | Mucosal | M1c | Exon 13 K642E | 8.86 | 1.1 | 2 | PD | 0.9 | 1.5 | Dead | NRAS G12A |
| 20 | Female | 66 | Mucosal | M1c | Exon 11 L576P | 12.25 | 2.6 | 4 | PR | 3.4 | 5.5 | Dead | |
| 21 | Female | 64 | Mucosal | M1c | Exon 11 V560D | N/T | N/T | 5 | PR | 4.5 | 9.1 | Dead | |
| 22 | Female | 42 | Acral-lentiginous | M1b | Exon 11 L576P | N/T | N/T | 3 | SD | 2.7 | 15.4 | Alive | |
| 23‡ | Female | 80 | Mucosal | M1c | Exon 13 K642E | N/T | N/T | 4 | SD | 3.5 | 10.6 | Alive | |
| 24 | Female | 73 | Mucosal | M1c | Exon 13 K642E | N/T | N/T | 8 | PR | 6.6 | 6.6 | Alive |
Abbreviations: FISH, fluorescent in situ hybridization; N/T, not tested; PCR, polymerase chain reaction; PD, progressive disease; PR, partial response; SD, stable disease.
The threshold for increased KIT copy number was set relative to normal samples with the 95% CI according to Chebychev's inequality; the formula used was mean ± (4.47 × standard deviation). The threshold for positive was 5.29 copies of KIT relative to glyceraldehyde 3-phosphate dehydrogenase.
KIT gene copy number was determined in relationship to a chromosome 2 pericentromeric probe, which corresponds to a region rarely subject to gain or loss in melanoma. A sample (or histologically distinctive region) was scored as amplified if the probe:centromere ratio was > 1.50 (highly amplified > 5.0).
Denotes those patients who underwent post-treatment biopsy for evaluation of resistance mechanisms.