Supplementary Table S1. Genetic aberrations of cells used in this studya
Cells / Cdk4 / Ccnd1 / P16INK4a / Brafb,c / Nrasb,cA2058 / Normal / Normal / Normal / V600E / WT
SK-Mel-5 / Normal / Gain / Loss / V600E / WT
AMC-1 / Gain / Normal / Normal / V600E / WT
AMC-2 / Normal / Gain / Normal / WT / WT
AMC-3 / Gain / Normal / Loss / WT / Q61R
AMC-4 / Normal / Normal / Loss / V600E / WT
AMC-5 / Normal / Normal / Normal / V600E / WT
Abbreviations: WT, wild type.
a The Kit gene in these cells is of wild-type.
b The amino acid aberration but not the nucleotide change was listed.
cThe hotspot regions (exons 11 and 15 of Braf gene, and exons 1 and 2 of Nras gene) of Braf and Nras were examined for mutations by PCR amplification of DNA followed by DNA sequencing (16).
1
Supplementary Table S2.Clinicopathological features and genetic aberrations of established PDX models used in this study
Code / Gender / Age / Ulceration / Thickness(mm) / Stage / Survival time (month) / Survival statusa / Cdk4 / Ccnd1 / P16INK4a / kitb,c / Brafb,c / Nras b,c
PDX-001 / F / 21 / Yes / 3.5 / IV / / / 1 / Gain / Gain / Normal / P551L / V600E/S607F / WT
PDX-006 / F / 63 / No / 3 / III / 27.0 / 0 / Gain / Normal / Normal / WT / WT / G12A
PDX-012 / M / 18 / Yes / 2 / II / 9.9 / 0 / Gain / Normal / Loss / WT / WT / WT
PDX-015 / M / 60 / Yes / 3 / III / 16.7 / 0 / Normal / Gain / Loss / WT / WT / WT
PDX-017 / M / 49 / Yes / 2.6 / IV / 6.3 / 0 / Normal / Normal / Normal / WT / WT / WT
Abbreviations: F, female; M, male; WT, wild type.
a “1” indicates survival, and “0” indicates for death.
b The amino acid aberration but not the nucleotide change was listed.
c The hotspot regions (exons 9, 11, 13, 17 and 18 of Kit gene, exons 11 and 15 of Braf gene, and exons 1 and 2 of Nras gene) of Kit, Braf and Nras were examined for mutations by PCR amplification of DNA followed by DNA sequencing (16, 17).
Supplementary Table S3. Detailed clinicopathological features and genetic aberrations of patients
Code / Gender / Age / Ulceration / Thickness (mm) / Stage / OS (month) / Survival statusa / CNV status (copy number)b / Genetic mutation statusc / IHC(year) / Cdk4 / Ccnd1 / P16INK4a / Kit / Braf / Nras / CDK4 / CCND1 / P16INK4a
2 / F / 35 / Yes / 9 / III / 28.5 / 1 / 5 / 2 / 2 / D572G, / WT / NA / NA / NA / NA
D820Y / NA / NA / NA
3 / M / 60 / Yes / 4 / III / 19.2 / 1 / 2 / 2 / 2 / WT / V600E, / NA / NA / NA / NA
S602F / NA / NA / NA
5 / M / 48 / Yes / 1.9 / III / 34.8 / 1 / 2 / 2 / 1 / WT / WT / NA / NA / NA / NA
8 / M / 37 / Yes / 1.5 / II / 55.3 / 0 / 1 / 1 / 0 / WT / WT / WT / NA / NA / NA
10 / F / 35 / Yes / 4 / II / 46.7 / 0 / 2 / 2 / 1 / WT / WT / NA / NA / NA / NA
11 / M / 48 / No / 8 / III / 46.7 / 1 / 4 / 3 / 0 / WT / WT / NA / NA / NA / NA
18 / F / 54 / Yes / 16 / II / 59 / 0 / 2 / 2 / 2 / WT / WT / NA / NA / NA / NA
21 / M / 35 / No / 2 / II / 31 / 0 / 2 / 3 / 0 / WT / WT / NA / NA / NA / NA
22 / M / 57 / No / 4 / II / 24.7 / 1 / 2 / 2 / 0 / WT / WT / NA / NA / NA / NA
29 / M / 43 / No / 5 / III / 74.4 / 0 / 2 / 2 / 2 / WT / WT / NA / NA / NA / NA
31 / F / 47 / No / 7 / II / 33 / 1 / 4 / 3 / 0 / WT / WT / NA / NA / NA / NA
36 / F / 63 / Yes / 1.5 / II / 52 / 0 / 4 / 2 / 2 / WT / WT / NA / NA / NA / NA
43 / M / 46 / Yes / 1.5 / III / 11.7 / 1 / 2 / 4 / 0 / WT / WT / WT / NA / NA / NA
49 / M / 60 / Yes / 8.5 / II / 21.3 / 1 / 2 / 1 / 1 / WT / WT / WT / 0 / 0 / 0
53 / M / 29 / Yes / 5 / III / 24.8 / 0 / 2 / 1 / 1 / WT / V600E / WT / 1 / 0 / 0
56 / F / 45 / No / 0.3 / I / 18.7 / 0 / 2 / 4 / 2 / WT / WT / WT / NA / NA / NA
58 / F / 47 / Yes / 1.1 / III / 11.5 / 0 / 2 / 2 / 2 / WT / V600E / WT / NA / NA / NA
65 / M / 67 / No / 1 / I / 8.7 / 0 / 2 / 3 / 2 / WT / WT / WT / NA / NA / NA
67 / M / 63 / No / 0.5 / I / 5.8 / 0 / 5 / 2 / 2 / WT / WT / WT / NA / NA / NA
70 / F / 46 / Yes / 1.2 / II / 8.6 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
85 / F / 48 / Yes / 2.5 / II / 48.4 / 0 / 1 / 1 / 0 / NA / WT / WT / NA / NA / NA
88 / M / 49 / Yes / 11 / II / 23.8 / 1 / 3 / 34 / 0 / K642E / WT / NA / NA / NA / NA
90 / M / 67 / Yes / 3.2 / II / 12.1 / 0 / 2 / 6 / 1 / WT / WT / NA / NA / NA / NA
91 / M / 64 / Yes / 5 / III / 62.3 / 1 / 2 / 1 / 2 / WT / WT / WT / NA / NA / NA
92 / M / 30 / Yes / 3 / II / 15.4 / 1 / 2 / 1 / 2 / WT / WT / WT / NA / NA / NA
94 / M / 54 / Yes / 2 / III / 26.1 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
97 / F / 58 / Yes / 3 / III / 51 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
101 / M / 55 / Yes / 12 / II / 46.7 / 0 / 3 / 5 / 2 / WT / WT / WT / NA / NA / NA
103 / F / 49 / No / 3 / II / 64.9 / 1 / 2 / 23 / 1 / WT / WT / NA / NA / NA / NA
114 / M / 70 / No / 2 / III / 133.3 / 0 / 2 / 23 / 1 / WT / WT / NA / NA / NA / NA
115 / F / 60 / Yes / 5 / II / 28.4 / 1 / 2 / 2 / 1 / WT / WT / NA / NA / NA / NA
118 / F / 64 / Yes / 6 / II / 47.1 / 0 / 2 / 2 / 2 / WT / WT / NA / NA / NA / NA
120 / M / 15 / No / 3.5 / III / 18.2 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
123 / F / 60 / Yes / 1.8 / II / 36.1 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
126 / M / 69 / Yes / 5 / II / 82.6 / 0 / 2 / 6 / 1 / WT / WT / WT / NA / NA / NA
128 / F / 62 / Yes / 4 / II / 82.6 / 1 / 5 / 2 / 1 / WT / WT / WT / NA / NA / NA
129 / F / 56 / Yes / 15 / II / 9.3 / 1 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
131 / F / 59 / Yes / 1.5 / II / 20.7 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
138 / M / 23 / Yes / 10 / III / 69.8 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
141 / F / 48 / Yes / 2.5 / II / 15.8 / 0 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
142 / F / 54 / Yes / 5 / II / 42.6 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
144 / M / 67 / No / 3 / III / 122.4 / 1 / 3 / 2 / 1 / WT / V600E / WT / NA / NA / NA
147 / M / 32 / No / 3 / III / 29.5 / 1 / 3 / 2 / 1 / WT / WT / NA / NA / NA / NA
148 / M / 57 / No / 3.6 / II / 17.3 / 1 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
149 / F / 42 / Yes / 6 / II / 54.1 / 1 / 2 / 2 / 2 / WT / V600E / WT / NA / NA / NA
150 / M / 55 / Yes / 6 / III / 45 / 1 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
151 / M / 61 / Yes / 3 / II / 80.2 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
153 / F / 61 / Yes / 2 / II / 53.7 / 1 / 2 / 2 / 1 / T574P / WT / G13R / NA / NA / NA
155 / F / 53 / Yes / 3 / II / 53.7 / 1 / 2 / 2 / 0 / WT / WT / WT / NA / NA / NA
156 / F / 49 / Yes / 7 / III / 23.7 / 1 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
157 / F / 29 / Yes / 2.2 / II / 40.8 / 1 / 15 / 2 / 0 / WT / WT / WT / NA / NA / NA
159 / F / 60 / Yes / 2 / II / 63.3 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
161 / M / 46 / Yes / 7 / III / 31.6 / 0 / 1 / 1 / 0 / WT / WT / NA / NA / NA / NA
163 / M / 51 / No / 2 / I / 41.7 / 0 / 2 / 3 / 1 / WT / V600E / G12D / NA / NA / NA
165 / M / 72 / Yes / 4 / III / 21.1 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
168 / M / 77 / Yes / 2 / II / 36.2 / 1 / 2 / 1 / 1 / L576P / WT / NA / NA / NA / NA
177 / M / 45 / No / 3 / II / 39 / 1 / 3 / 3 / 0 / WT / WT / NA / NA / NA / NA
181 / F / 51 / Yes / 9 / III / 39.6 / 0 / 3 / 3 / 0 / WT / V600E / WT / NA / NA / NA
186 / F / 55 / Yes / 7 / II / 17.9 / 1 / 3 / 1 / 0 / WT / WT / WT / NA / NA / NA
187 / M / 62 / Yes / 3 / III / 11.6 / 1 / 2 / 2 / 2 / WT / WT / NA / NA / NA / NA
189 / F / 61 / Yes / 2 / II / 39.7 / 0 / 2 / 2 / 2 / WT / WT / Q61R / NA / NA / NA
190 / M / 75 / Yes / 5 / IV / 20.3 / 1 / 2 / 1 / 0 / WT / WT / WT / NA / NA / NA
191 / M / 43 / Yes / 5 / III / 28 / 1 / 2 / 12 / 1 / WT / WT / WT / NA / NA / NA
192 / M / 54 / Yes / 3 / II / 30 / 1 / 8 / 2 / 2 / WT / WT / WT / NA / NA / NA
193 / M / 49 / Yes / 6 / II / 56 / 1 / 9 / 3 / 1 / WT / WT / WT / NA / NA / NA
195 / M / 56 / Yes / 8 / III / 43.2 / 1 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
198 / M / 44 / No / 4 / II / 48.6 / 1 / 2 / 2 / 0 / WT / WT / NA / NA / NA / NA
199 / M / 54 / Yes / 2 / IV / 6 / 1 / 2 / 2 / 1 / WT / WT / NA / NA / NA / NA
200 / F / 67 / Yes / 3 / II / 24 / 0 / 2 / 2 / 1 / WT / WT / NA / NA / NA / NA
201 / F / 61 / Yes / 5 / II / 12.8 / 1 / 2 / 3 / 2 / WT / WT / NA / NA / NA / NA
202 / M / 71 / Yes / 10 / III / 32.3 / 1 / 4 / 1 / 0 / WT / V600E / WT / NA / NA / NA
204 / M / 62 / Yes / 7 / II / 39.6 / 0 / 2 / 8 / 2 / WT / WT / NA / NA / NA / NA
205 / F / 71 / Yes / 1.5 / II / 38.4 / 1 / 2 / 2 / 0 / WT / WT / NA / NA / NA / NA
206 / M / 29 / Yes / 2 / III / 19.1 / 0 / 2 / 2 / 1 / WT / V600E / WT / NA / NA / NA
207 / F / 30 / No / 2 / II / 42 / 1 / 2 / 2 / 1 / WT / WT / NA / NA / NA / NA
209 / M / 82 / Yes / 1.3 / II / 28.3 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
213 / F / 64 / No / 1 / I / 37.5 / 0 / 2 / 2 / 2 / WT / WT / NA / NA / NA / NA
215 / M / 57 / Yes / 2 / II / 38.7 / 0 / 3 / 2 / 2 / WT / WT / NA / NA / NA / NA
218 / F / 58 / Yes / 3 / III / 63.7 / 1 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
220 / F / 64 / Yes / 2 / III / 170.9 / 0 / 2 / 3 / 3 / WT / WT / NA / NA / NA / NA
221 / F / 57 / No / 4.5 / II / 74.9 / 1 / 5 / 45 / 1 / WT / WT / NA / NA / NA / NA
225 / M / 72 / Yes / 12 / II / 15.4 / 0 / 2 / 2 / 1 / H630D / WT / NA / 2 / 0 / 1
232 / M / 57 / Yes / 1.8 / III / 37 / 1 / 2 / 2 / 2 / WT / WT / NA / NA / NA / NA
233 / M / 29 / Yes / 1.5 / II / 34.3 / 0 / 2 / 2 / 2 / WT / V600E / NA / NA / NA / NA
236 / F / 50 / Yes / 1.1 / II / 63.8 / 1 / 2 / 2 / 0 / K642E / WT / NA / NA / NA / NA
239 / F / 44 / Yes / 6 / II / 61.4 / 1 / 3 / 2 / 2 / WT / V600E / NA / NA / NA / NA
240 / M / 56 / No / 2 / I / 18.2 / 1 / 3 / 3 / 1 / WT / V600E / NA / NA / NA / NA
241 / F / 74 / No / 7.5 / III / 56.1 / 1 / 3 / 1 / 1 / WT / WT / WT / NA / NA / NA
243 / M / 63 / Yes / 9 / II / 35 / 0 / 10 / 8 / 2 / WT / V600K / WT / NA / NA / NA
244 / F / 58 / No / 0.9 / I / 35 / 0 / 4 / 2 / 2 / WT / WT / WT / NA / NA / NA
246 / M / 74 / Yes / 5 / II / 27.4 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
247 / F / 52 / Yes / 4 / III / 35.2 / 0 / 2 / 5 / 2 / WT / NA / WT / NA / NA / NA
248 / M / 37 / Yes / 11 / III / 11.4 / 1 / 2 / 1 / 1 / WT / WT / Q61R / NA / NA / NA
249 / F / 58 / Yes / 1.7 / II / 25.7 / 1 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
250 / M / 64 / Yes / 2.6 / IV / 40.9 / 1 / 2 / 2 / 0 / WT / WT / WT / NA / NA / NA
253 / M / 46 / No / 1 / I / 38.2 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
254 / M / 42 / Yes / 4 / II / 34.8 / 1 / 3 / 1 / 1 / WT / WT / WT / NA / NA / NA
255 / F / 63 / No / 1.2 / II / 38 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
257 / F / 44 / No / 5 / II / 44.6 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
258 / F / 78 / Yes / 2 / III / 35.1 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
261 / M / 64 / Yes / 12 / IV / 5.4 / 1 / 3 / 1 / 0 / WT / V600E / WT / 1 / 0 / 0
262 / M / 72 / Yes / 18 / IV / 12 / 1 / 4 / 27 / 0 / WT / WT / WT / NA / NA / NA
264 / F / 50 / No / 7 / II / 25.1 / 1 / 14 / 2 / 3 / WT / WT / WT / NA / NA / NA
266 / M / 77 / Yes / 0.5 / I / 18.3 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
268 / F / 43 / Yes / 1 / I / 32.9 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
269 / F / 73 / Yes / 5 / II / 34.1 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
270 / M / 59 / No / 5 / III / 39.9 / 0 / 3 / 4 / 2 / WT / WT / NA / NA / NA / NA
271 / M / 43 / Yes / 2 / II / 39.6 / 0 / 2 / 2 / 0 / WT / V600E / WT / NA / NA / NA
273 / M / 77 / No / 6.8 / IV / 10.1 / 1 / 4 / 2 / 0 / WT / WT / WT / NA / NA / NA
274 / M / 49 / Yes / 10 / III / 15.2 / 1 / 3 / 8 / 1 / WT / WT / WT / NA / NA / NA
276 / F / 69 / Yes / 5 / IV / 14.5 / 1 / 2 / 2 / 0 / WT / WT / WT / NA / NA / NA
278 / M / 69 / Yes / 2.5 / III / 8.1 / 1 / 2 / 7 / 1 / WT / WT / WT / NA / NA / NA
279 / M / 44 / Yes / 2 / II / 33 / 1 / 12 / 0 / 1 / WT / K601K / WT / 1 / 0 / 0
280 / M / 60 / Yes / 5 / II / 36.8 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
281 / M / 55 / Yes / 3.5 / II / 32.8 / 0 / 6 / 2 / 2 / WT / WT / WT / NA / NA / NA
282 / M / 42 / Yes / 8 / II / 20.4 / 1 / 3 / 1 / 2 / WT / WT / WT / NA / NA / NA
283 / F / 65 / Yes / 1.3 / II / 31.9 / 0 / 2 / 2 / 2 / WT / WT / G12S / NA / NA / NA
284 / M / 72 / Yes / 6.5 / II / 33.9 / 1 / 3 / 2 / 0 / WT / WT / Q61R / 2 / 0 / 0
285 / M / 76 / No / 5 / II / 33.9 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
287 / F / 50 / Yes / 9 / IV / 8.9 / 1 / 2 / 2 / 1 / WT / WT / WT / 1 / 0 / 1
288 / M / 60 / Yes / 6 / II / 46.9 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
289 / F / 58 / Yes / 6 / III / 32 / 0 / 2 / 2 / 1 / E861K / V600E / WT / 1 / 0 / 0
290 / M / 42 / Yes / 5 / II / 35.8 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
291 / M / 31 / Yes / 1.5 / II / 95.1 / 1 / 2 / 1 / 1 / WT / WT / WT / 2 / 0 / 0
292 / M / 56 / Yes / 2 / III / 76.5 / 0 / 2 / 4 / 2 / WT / WT / I24T, / NA / NA / NA
N26S, / NA / NA / NA
A83V / NA / NA / NA
293 / M / 68 / Yes / 2 / II / 34.3 / 0 / 2 / 2 / 2 / WT / WT / G12D / NA / NA / NA
294 / F / 34 / Yes / 7 / II / 33.3 / 0 / 5 / 3 / 2 / WT / WT / WT / NA / NA / NA
296 / M / 70 / Yes / 23 / IV / 10.3 / 1 / 3 / 3 / 2 / WT / WT / WT / NA / NA / NA
297 / M / 69 / Yes / 6 / III / 33 / 0 / 2 / 2 / 1 / R586G / V600E / WT / 2 / 1 / 0
298 / M / 61 / Yes / 1.8 / II / 33.9 / 1 / 3 / 3 / 1 / W557R / WT / WT / NA / NA / NA
299 / M / 69 / Yes / 7 / II / 31.6 / 0 / 2 / 2 / 1 / WT / WT / WT / 2 / 1 / 0
300 / M / 47 / Yes / 0.6 / I / 32.9 / 0 / 3 / 3 / 2 / WT / WT / WT / NA / NA / NA
301 / F / 60 / Yes / 1.8 / III / 12.1 / 1 / 2 / 2 / 0 / T488M / WT / Q61R / 0 / 2 / 0
302 / M / 52 / Yes / 6 / III / 26 / 1 / 3 / 6 / 0 / WT / WT / WT / NA / NA / NA
303 / F / 63 / Yes / 2 / II / 41.9 / 1 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
304 / M / 53 / No / 1 / I / 33.4 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
305 / M / 74 / Yes / 8 / II / 106.1 / 0 / 25 / 2 / 2 / WT / WT / WT / NA / NA / NA
306 / F / 41 / Yes / 10 / III / 33 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
307 / M / 48 / No / 2 / III / 37 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
308 / F / 65 / Yes / 3 / IV / 29.4 / 1 / 2 / 2 / 1 / G648D / WT / WT / 2 / 0 / 1
309 / F / 23 / Yes / 6 / II / 20.8 / 1 / 3 / 2 / 3 / WT / WT / WT / 2 / 2 / 2
310 / M / 51 / No / 2.1 / IV / 43.6 / 1 / 2 / 4 / 1 / F483I / WT / WT / NA / NA / NA
311 / M / 84 / Yes / 8.5 / II / 17.8 / 1 / 3 / 2 / 2 / WT / WT / Q61L / NA / NA / 0
312 / F / 40 / Yes / 6 / II / 31.7 / 1 / 14 / 1 / 1 / WT / WT / G12D, / 2 / 1 / 1
F82S / NA / NA / NA
313 / F / 54 / No / 3.5 / II / 43.6 / 0 / 2 / 2 / 0 / F483I / WT / WT / 1 / 1 / 0
315 / F / 23 / No / 5 / II / 32.8 / 0 / 2 / 2 / 1 / WT / WT / WT / 2 / 1 / 1
316 / M / 50 / Yes / 2.5 / IV / 14.1 / 1 / 2 / 33 / 2 / WT / WT / WT / NA / NA / NA
317 / M / 58 / Yes / 11 / III / 47 / 1 / 3 / 6 / 1 / WT / WT / WT / 2 / 2 / 0
319 / M / 60 / Yes / 3 / II / 40.3 / 0 / 2 / 2 / 1 / K642E / WT / WT / NA / NA / NA
320 / F / 42 / Yes / 7 / II / 39.5 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
321 / F / 39 / Yes / 6.5 / II / 23.8 / 1 / 7 / 2 / 2 / H630N / WT / Q61R / NA / NA / NA
322 / M / 65 / Yes / 5 / II / 44 / 0 / 13 / 1 / 2 / P573S / V600E / WT / NA / NA / NA
323 / F / 57 / Yes / 12 / IV / 23.8 / 1 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
324 / M / 51 / Yes / 4 / II / 42.2 / 1 / 8 / 2 / 1 / K471R, / WT / WT / NA / NA / NA
L576P / NA / NA / NA
325 / M / 44 / Yes / 15 / II / 59.1 / 1 / 2 / 2 / 0 / WT / WT / WT / NA / NA / NA
326 / M / 53 / No / 3 / II / 31.9 / 0 / 2 / 2 / 1 / WT / WT / WT / 1 / 0 / 1
327 / M / 59 / Yes / 3 / II / 53.6 / 1 / 3 / 4 / 2 / WT / WT / WT / NA / NA / NA
329 / F / 46 / Yes / 13 / II / 31.5 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
330 / M / 66 / No / 2 / I / 31.8 / 0 / 4 / 3 / 2 / A829P / WT / WT / NA / NA / NA
332 / M / 39 / No / 2 / III / 31.9 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
333 / F / 50 / No / 1.5 / I / 31 / 0 / 2 / 2 / 1 / WT / WT / WT / 1 / 1 / 3
335 / M / 47 / Yes / 4.5 / III / 24.8 / 1 / 25 / 7 / 2 / WT / WT / WT / NA / NA / NA
336 / M / 53 / NA / 0.2 / IV / 37 / 1 / 3 / 0 / 2 / WT / WT / WT / NA / NA / NA
337 / F / 45 / Yes / 5 / II / 36 / 1 / 3 / 3 / 1 / WT / V600E / WT / NA / NA / NA
338 / M / 55 / Yes / 1 / I / 50.1 / 0 / 2 / 46 / 2 / WT / WT / WT / NA / NA / NA
339 / M / 52 / Yes / 4 / II / 46 / 0 / 15 / 2 / 2 / WT / WT / WT / NA / NA / NA
340 / F / 70 / Yes / 5 / III / 36.8 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
341 / M / 35 / Yes / 2 / II / 33 / 0 / 2 / 2 / 1 / WT / V600E / WT / 1 / 0 / 0
342 / F / 49 / NA / 9 / IV / 19 / 1 / 3 / 2 / 2 / WT / WT / Q61R / NA / NA / NA
343 / M / 51 / No / 1 / III / 29.4 / 0 / 3 / 2 / 2 / WT / WT / Q61L / NA / NA / NA
345 / F / 50 / Yes / 3 / II / 29.6 / 0 / 2 / 1 / 0 / WT / WT / Q70S / 0 / 2 / 0
346 / F / 66 / Yes / 11 / II / 32 / 1 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
347 / M / 46 / No / 5 / II / 29.8 / 0 / 2 / 1 / 0 / WT / WT / WT / NA / NA / NA
348 / F / 55 / No / 2 / I / 3 / 0 / 3 / 5 / 1 / WT / WT / Q61K / NA / NA / NA
349 / M / 55 / Yes / 18 / III / 20.7 / 1 / 2 / 2 / 2 / N822K / WT / WT / NA / NA / NA
350 / F / 15 / No / 7.8 / IV / 9.4 / 1 / 3 / 2 / 1 / WT / WT / WT / 1 / 0 / 0
351 / F / 39 / Yes / 1.5 / IV / 20.8 / 1 / 2 / 2 / 1 / WT / WT / WT / 1 / 1 / 0
352 / M / 59 / No / 3 / II / 30 / 0 / 3 / 2 / 0 / WT / WT / WT / 2 / 1 / 1
357 / M / 35 / Yes / 20 / II / 68.8 / 0 / 3 / 45 / 2 / WT / WT / WT / NA / NA / NA
358 / F / 53 / Yes / 15 / IV / 24.6 / 0 / 2 / 3 / 0 / WT / WT / WT / NA / NA / NA
359 / M / 64 / No / 7.8 / II / 121.2 / 1 / 14 / 1 / 1 / N822H / WT / WT / NA / NA / NA
360 / F / 62 / Yes / 1.5 / II / 28.8 / 0 / 5 / 2 / 1 / WT / V600E / WT / 2 / 0 / 1
361 / M / 67 / Yes / 2 / IV / 30.4 / 1 / 3 / 4 / 1 / WT / WT / WT / NA / NA / NA
362 / F / 64 / No / 7 / II / 29.8 / 0 / 3 / 5 / 0 / WT / WT / WT / NA / NA / NA
363 / M / 52 / Yes / 5 / III / 28.4 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
365 / M / 41 / Yes / 1 / III / 29.2 / 0 / 3 / 18 / 1 / WT / WT / Q61L / NA / NA / NA
366 / M / 67 / Yes / 5 / III / 100.7 / 1 / 3 / 2 / 0 / WT / WT / WT / 1 / 0 / 0
367 / M / 46 / No / 8.5 / III / 29 / 0 / 3 / 3 / 1 / WT / WT / Q61K / NA / NA / NA
368 / F / 50 / No / 1 / III / 29.2 / 0 / 2 / 1 / 2 / WT / WT / Q61R / NA / NA / NA
369 / F / 46 / No / 7 / IV / 8 / 1 / 3 / 2 / 1 / WT / WT / Q61R / 1 / 2 / 0
370 / F / 75 / Yes / 5 / IV / 16 / 1 / 22 / 2 / 1 / WT / WT / NA / 2 / 1 / 0
372 / M / 57 / Yes / 5 / III / 29.5 / 0 / 16 / 2 / 0 / WT / WT / WT / NA / NA / NA
373 / F / 48 / No / 1.2 / I / 29.9 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
374 / M / 53 / Yes / 1.2 / IV / 28.3 / 1 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
376 / M / 62 / No / 3 / III / 16 / 1 / 2 / 8 / 2 / WT / WT / WT / NA / NA / NA
377 / M / 58 / No / 2.8 / II / 29.8 / 0 / 2 / 1 / 1 / WT / WT / WT / 0 / 0 / 1
378 / F / 43 / Yes / 10 / II / 27.1 / 0 / 20 / 4 / 2 / K642E / WT / WT / NA / NA / NA
379 / M / 53 / Yes / 7 / II / 82.6 / 0 / 64 / 7 / 2 / WT / WT / NA / NA / NA / NA
380 / M / 64 / Yes / 12 / II / 17.5 / 1 / 3 / 1 / 0 / WT / WT / WT / NA / NA / NA
382 / M / 61 / Yes / 15 / III / 27 / 0 / 8 / 2 / 1 / L576P / WT / WT / NA / NA / NA
383 / F / 64 / Yes / 1.3 / II / 34 / 0 / 3 / 1 / 1 / WT / WT / WT / 1 / 0 / 0
384 / M / 72 / Yes / 4 / III / 28.9 / 0 / 2 / 2 / 1 / WT / WT / WT / 1 / 0 / 0
385 / M / 50 / Yes / 5 / III / 29 / 1 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
386 / M / 46 / Yes / 11 / IV / 22.3 / 1 / 2 / 1 / 1 / WT / WT / WT / 1 / 1 / 0
387 / M / 50 / Yes / 6 / III / 78.6 / 1 / 11 / 2 / 2 / WT / WT / K67T / NA / NA / NA
388 / F / 45 / Yes / 3 / II / 45.8 / 1 / 3 / 1 / 1 / WT / WT / WT / 2 / 0 / 0
389 / M / 43 / No / 3.5 / IV / 7.5 / 1 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
390 / F / 61 / Yes / 10 / III / 21.5 / 1 / 2 / 1 / 1 / WT / WT / Q61R / 0 / 0 / 0
391 / F / 52 / No / 5 / II / 152.8 / 1 / 37 / 5 / 0 / WT / WT / WT / NA / NA / NA
392 / M / 56 / Yes / 6 / III / 40.3 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / 0
393 / M / 82 / Yes / 5 / II / 15 / 0 / 3 / 2 / 1 / WT / V600E / WT / NA / NA / 0
394 / F / 69 / Yes / 15 / II / 69.8 / 1 / 2 / 2 / 1 / WT / WT / WT / 1 / 0 / 1
395 / F / 61 / Yes / 3.5 / III / 20 / 1 / 3 / 2 / 1 / WT / WT / Q61R / NA / NA / 0
396 / M / 57 / Yes / 5 / II / 18.7 / 1 / 2 / 2 / 1 / WT / WT / Q61R / NA / NA / 0
397 / M / 65 / Yes / 3 / II / 27.9 / 0 / 2 / 1 / 1 / WT / WT / WT / 0 / 2 / 1
398 / M / 52 / Yes / 6 / II / 60 / 1 / 9 / 1 / 0 / WT / G615G / WT / 1 / 1 / 0
399 / F / 51 / Yes / 2 / III / 17.1 / 1 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
401 / F / 47 / Yes / 5 / IV / 26.1 / 0 / 2 / 6 / 1 / WT / WT / Q61H / NA / NA / NA
402 / M / 70 / Yes / 5 / II / 45.2 / 0 / 2 / 1 / 0 / WT / WT / Q61R / NA / NA / NA
403 / F / 28 / Yes / 3 / III / 30.2 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
404 / M / 30 / Yes / 6.4 / II / 22.5 / 1 / 3 / 1 / 2 / WT / V600E / WT / NA / NA / NA
405 / M / 60 / Yes / 5 / II / 25.5 / 0 / 2 / 2 / 1 / WT / WT / WT / 2 / 3 / 0
407 / M / 49 / Yes / 3 / III / 25.9 / 0 / 2 / 2 / 1 / WT / V600E / WT / 2 / 0 / 0
409 / M / 72 / Yes / 2 / II / 31.6 / 1 / 5 / 1 / 1 / L576P / WT / WT / NA / NA / NA
410 / F / 72 / Yes / 1 / I / 33.6 / 1 / 3 / 3 / 1 / WT / WT / Q61R / NA / NA / NA
411 / F / 80 / Yes / 10 / II / 8 / 1 / 3 / 3 / 0 / L576P / WT / WT / NA / NA / NA
412 / M / 59 / No / 7.8 / III / 37 / 0 / 3 / 3 / 2 / WT / V600E / WT / NA / NA / NA
415 / F / 54 / Yes / 15 / II / 70 / 0 / 2 / 2 / 1 / WT / WT / WT / 2 / 3 / 0
416 / F / 48 / No / 13 / I / 125.3 / 0 / 3 / 3 / 1 / WT / WT / WT / NA / NA / NA
419 / M / 81 / No / 7 / II / 12 / 1 / 10 / 2 / 2 / WT / WT / WT / NA / NA / NA
420 / M / 30 / Yes / 1.5 / III / 26.9 / 0 / 2 / 3 / 2 / WT / WT / WT / NA / NA / NA
422 / M / 46 / Yes / 5 / III / 37 / 0 / 2 / 2 / 0 / WT / V600E / WT / 2 / 1 / 0
426 / M / 73 / Yes / 4 / II / 25.9 / 0 / 2 / 3 / 2 / WT / WT / WT / NA / NA / NA
427 / M / 46 / Yes / 4.5 / III / 25.8 / 0 / 2 / 2 / 1 / WT / V600E / WT / 3 / 2 / 0
430 / M / 55 / Yes / 2 / III / 24 / 0 / 2 / 15 / 2 / WT / WT / WT / NA / NA / NA
434 / M / 66 / Yes / 4 / III / 23.5 / 0 / 3 / 6 / 1 / WT / WT / WT / NA / NA / NA
435 / F / 55 / Yes / 2 / III / 56 / 0 / 2 / 2 / 1 / WT / WT / WT / 3 / 1 / 0
436 / M / 60 / Yes / 3 / II / 23.5 / 0 / 2 / 3 / 1 / WT / WT / WT / NA / NA / NA
437 / F / 45 / Yes / 1.4 / II / 24 / 0 / 2 / 2 / 1 / WT / V600E / WT / 1 / 2 / 1
439 / F / 72 / Yes / 1.6 / II / 53.2 / 0 / 2 / 1 / 0 / WT / V600E / WT / NA / NA / NA
440 / M / 31 / Yes / 2 / II / 21.9 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
443 / M / 43 / No / 1 / I / 22.5 / 0 / 2 / 4 / 2 / WT / WT / WT / NA / NA / NA
444 / F / 24 / Yes / 5 / II / 22.2 / 0 / 3 / 3 / 1 / WT / V600E / WT / NA / NA / NA
445 / F / 39 / Yes / 2 / I / 22.5 / 0 / 14 / 2 / 2 / N822K / WT / WT / NA / NA / NA
446 / F / 42 / Yes / 1 / III / 50 / 0 / 2 / 2 / 1 / WT / V600E / WT / NA / NA / NA
447 / F / 60 / Yes / 8 / II / 23.7 / 0 / 15 / 3 / 1 / WT / WT / WT / NA / NA / NA
448 / F / 79 / Yes / 6 / II / 123 / 1 / 4 / 2 / 2 / WT / WT / WT / NA / NA / NA
452 / F / 59 / No / 7 / II / 24.9 / 0 / 17 / 2 / 2 / WT / WT / WT / NA / NA / NA
453 / M / 20 / Yes / 5 / II / 23.1 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
454 / F / 49 / Yes / 3 / II / 22.2 / 0 / 3 / 1 / 1 / WT / V600E / WT / NA / NA / NA
455 / F / 44 / No / 5 / II / 22.2 / 0 / 2 / 2 / 1 / WT / V600E / WT / NA / NA / NA
456 / M / 71 / No / 8 / II / 22.3 / 0 / 8 / 3 / 1 / WT / G596R / WT / 2 / 2 / 0
458 / M / 63 / No / 6 / III / 20.8 / 0 / 2 / 3 / 1 / WT / WT / Q61R / 0 / 1 / 0
459 / M / 68 / Yes / 1.2 / IV / 21 / 0 / 2 / 2 / 1 / D572Y / WT / WT / 1 / 2 / 1
460 / F / 52 / No / 2 / I / 21.3 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
462 / F / 45 / Yes / 12 / II / 20.5 / 0 / 3 / 3 / 2 / WT / V600E / WT / NA / NA / NA
463 / M / 50 / No / 1 / I / 21.7 / 0 / 3 / 2 / 1 / L576P / WT / WT / 3 / 0 / 0
465 / M / 51 / Yes / 6 / III / 16.8 / 1 / 2 / 2 / 2 / WT / V600E / WT / 2 / 0 / 2
469 / M / 74 / Yes / 12 / III / 21.5 / 0 / 3 / 2 / 0 / WT / WT / Q61R / 3 / 1 / 1
470 / F / 56 / Yes / 4 / II / 21.1 / 0 / 4 / 2 / 2 / WT / WT / WT / NA / NA / NA
471 / M / 51 / No / 2.5 / II / 21.4 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
472 / M / 78 / Yes / 6 / II / 30.8 / 0 / 2 / 5 / 2 / WT / WT / WT / NA / NA / NA
473 / M / 52 / Yes / 6 / III / 20.3 / 0 / 2 / 3 / 1 / S476I / WT / WT / NA / NA / NA
476 / F / 64 / Yes / 1.1 / II / 20.6 / 0 / 2 / 2 / 1 / WT / WT / Q61R / 3 / 0 / 0
477 / M / 71 / Yes / 3 / IV / 8.1 / 1 / 2 / 2 / 2 / WT / V600E / WT / NA / NA / NA
478 / M / 43 / Yes / 5 / III / 20.6 / 0 / 4 / 6 / 2 / WT / WT / WT / NA / NA / NA
479 / F / 48 / Yes / 1.8 / II / 21.9 / 0 / 2 / 2 / 2 / WT / WT / Q61R / NA / NA / NA
481 / F / 35 / Yes / 3 / IV / 24 / 1 / 2 / 1 / 0 / WT / WT / E49G / 1 / 2 / 1
484 / M / 45 / No / 3 / III / 20.8 / 0 / 2 / 6 / 1 / WT / V600E / WT / 2 / 1 / 0
485 / F / 52 / Yes / 3 / II / 34.8 / 0 / 3 / 3 / 2 / WT / V600E / WT / NA / NA / NA
487 / F / 56 / Yes / 1.6 / II / 20.3 / 0 / 2 / 2 / 2 / WT / WT / Q61K / NA / NA / NA
489 / F / 75 / Yes / 1 / I / 20.3 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
490 / M / 49 / No / 1 / I / 26 / 0 / 2 / 0 / 1 / WT / WT / WT / NA / NA / NA
491 / M / 59 / Yes / 3.2 / IV / 26.1 / 1 / 3 / 8 / 1 / D820Y / WT / WT / NA / NA / NA
493 / F / 67 / Yes / 4.8 / II / 20.5 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
494 / F / 39 / Yes / 5 / II / 19.6 / 0 / 2 / 1 / 1 / WT / WT / WT / 3 / 0 / 0
495 / M / 43 / No / 0.1 / I / 20 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
498 / F / 72 / No / 5 / II / 19.3 / 0 / 3 / 3 / 2 / WT / WT / WT / NA / NA / NA
499 / F / 25 / No / 1.1 / I / 19.5 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
500 / M / 69 / Yes / 3 / II / 20.6 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
501 / F / 38 / No / 8 / II / 55.8 / 1 / 3 / 2 / 1 / WT / V600E / WT / 3 / 2 / 0
502 / F / 28 / Yes / 7 / III / 19.5 / 1 / 2 / 2 / 0 / WT / WT / Q61H / 3 / 1 / 1
504 / M / 53 / Yes / 3 / III / 20.8 / 0 / 4 / 5 / 2 / WT / WT / WT / NA / NA / NA
505 / M / 76 / Yes / 8 / II / 20.3 / 0 / 13 / 2 / 2 / WT / WT / WT / NA / NA / NA
508 / F / 61 / Yes / 9 / III / 18.8 / 0 / 2 / 2 / 1 / WT / WT / Q61R / 2 / 0 / 1
509 / F / 60 / Yes / 2.9 / II / 19.7 / 0 / 10 / 2 / 2 / K642E / WT / WT / NA / NA / NA
510 / M / 47 / Yes / 17 / III / 41.4 / 1 / 3 / 2 / 1 / WT / WT / Q61R / 2 / 1 / 1
511 / F / 50 / No / 7 / II / 40 / 1 / 9 / 2 / 1 / WT / WT / Q61R / 2 / 2 / 0
512 / F / 59 / NA / 3.5 / II / 26 / 0 / 4 / 3 / 1 / WT / V600E / WT / NA / NA / NA
513 / M / 58 / No / 5 / II / 28 / 0 / 2 / 59 / 2 / WT / WT / WT / NA / NA / NA
514 / M / 72 / No / 1 / III / 19 / 1 / 3 / 49 / 1 / WT / WT / WT / NA / NA / NA
517 / M / 68 / No / 0.85 / II / 22 / 0 / 2 / 2 / 1 / WT / V600E / WT / 0 / 0 / 0
518 / M / 51 / No / 2.4 / II / 18.3 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
519 / M / 70 / Yes / 3 / II / 18.2 / 0 / 5 / 2 / 2 / WT / WT / WT / NA / NA / NA
520 / M / 89 / No / 3 / II / 23.7 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
522 / F / 42 / Yes / 6 / II / 19.7 / 0 / 3 / 2 / 1 / WT / V600E / WT / NA / NA / NA
527 / M / 62 / Yes / 3.7 / III / 29.9 / 0 / 3 / 7 / 1 / WT / WT / WT / NA / NA / NA
528 / M / 37 / No / 3.4 / III / 11.7 / 1 / 2 / 3 / 1 / WT / WT / WT / 2 / 2 / 0
529 / F / 77 / Yes / 6 / IV / 19.8 / 1 / 4 / 2 / 1 / WT / WT / WT / 3 / 0 / 1
532 / M / 35 / Yes / 4 / II / 37 / 1 / 2 / 2 / 1 / WT / V600E / WT / 3 / 0 / 0
533 / M / 68 / Yes / 1.8 / II / 15.7 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
534 / F / 78 / No / 2.1 / III / 31 / 1 / 2 / 2 / 1 / WT / WT / Q61K / 1 / 0 / 1
535 / M / 62 / Yes / 1.9 / III / 20.6 / 0 / 2 / 2 / 0 / WT / WT / WT / 2 / 0 / 2
536 / M / 59 / No / 5 / IV / 13.2 / 1 / 3 / 2 / 2 / K642E / WT / WT / NA / NA / NA
537 / M / 59 / Yes / 4.8 / II / 17.2 / 0 / 37 / 3 / 1 / WT / V600E / WT / NA / NA / NA
538 / M / 51 / No / 1.4 / III / 16.7 / 0 / 3 / 3 / 1 / WT / WT / Q61R / 1 / 2 / 1
539 / F / 35 / Yes / 9.5 / II / 43 / 1 / 3 / 2 / 2 / K642E / WT / WT / NA / NA / NA
540 / M / 45 / Yes / 12 / II / 43 / 0 / 2 / 4 / 0 / WT / WT / WT / NA / NA / NA
541 / F / 67 / No / 3 / II / 18.3 / 0 / 2 / 2 / 2 / WT / WT / Q61R / NA / NA / NA
542 / M / 40 / Yes / 5 / III / 18.2 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
543 / F / 57 / No / 7.2 / IV / 17.9 / 1 / 3 / 1 / 2 / WT / WT / WT / 2 / 3 / 2
544 / M / 64 / Yes / 14 / IV / 27.8 / 0 / 3 / 1 / 1 / WT / WT / WT / 2 / 2 / 1
545 / M / 73 / No / 1 / IV / 79.8 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
546 / M / 32 / No / 0.6 / I / 18.2 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
547 / M / 48 / Yes / 4 / III / 20.1 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
548 / F / 64 / No / 1.5 / I / 35.9 / 0 / 2 / 2 / 1 / WT / WT / WT / 3 / 3 / 2
549 / F / 31 / No / 1 / I / 19.2 / 0 / 2 / 2 / 2 / WT / WT / Q61K / NA / NA / NA
550 / F / 63 / Yes / 0.5 / I / 17.7 / 0 / 3 / 3 / 2 / WT / V600E / WT / NA / NA / NA
564 / F / 65 / Yes / 3 / III / 43.3 / 1 / 2 / 2 / 1 / WT / WT / NA / 0 / 0 / 0
567 / M / 44 / Yes / 1.5 / II / 5.4 / 0 / 3 / 2 / 1 / WT / WT / WT / 1 / 2 / 0
580 / M / 52 / No / 6 / IV / 6 / 1 / 2 / 2 / 1 / WT / WT / WT / 3 / 0 / 0
582 / F / 70 / Yes / 4.2 / II / 12.5 / 0 / 2 / 2 / 1 / WT / WT / WT / 1 / 0 / 0
583 / F / 58 / No / 3 / II / 21 / 0 / 0 / 0 / 0 / WT / WT / WT / 1 / 1 / 0
584 / M / 73 / Yes / 4 / II / 14.6 / 0 / 2 / 3 / 1 / WT / WT / WT / NA / NA / NA
585 / M / 65 / Yes / 2.4 / IV / 12 / 0 / 2 / 2 / 2 / L576P / WT / WT / NA / NA / NA
586 / F / 65 / Yes / 1.6 / III / 12.3 / 0 / 2 / 1 / 0 / WT / V600E / Q61R / NA / NA / NA
587 / F / 72 / Yes / 5 / III / 17 / 1 / 2 / 2 / 1 / WT / WT / WT / 1 / 0 / 0
588 / F / 69 / Yes / 6.5 / II / 10.4 / 0 / 2 / 1 / 0 / V654A / NA / Q61R / 3 / 2 / 2
589 / F / 64 / Yes / 5 / II / 69.2 / 1 / 5 / 4 / 1 / WT / WT / WT / NA / NA / NA
590 / M / 45 / Yes / 0.9 / I / 10.8 / 0 / 2 / 1 / 1 / S476I / WT / WT / NA / NA / NA
591 / F / 69 / Yes / 7 / IV / 10.1 / 0 / 9 / 1 / 1 / WT / WT / WT / NA / NA / NA
592 / M / 81 / Yes / 5 / II / 8.6 / 1 / 10 / 5 / 1 / WT / V600E / WT / NA / NA / NA
593 / M / 81 / Yes / 4 / II / 11.5 / 0 / 4 / 2 / 1 / WT / WT / WT / 3 / 3 / 2
594 / F / 60 / No / 1.5 / II / 11.9 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
595 / F / 63 / Yes / 3 / II / 11.5 / 0 / 2 / 6 / 0 / K642E / WT / WT / 3 / 2 / 0
596 / F / 55 / Yes / 8 / II / 11.5 / 0 / 3 / 2 / 2 / WT / WT / Q61R / NA / NA / NA
597 / M / 62 / Yes / 1.2 / III / 11 / 0 / 2 / 2 / 1 / WT / WT / WT / 0 / 0 / 0
598 / M / 77 / Yes / 5 / II / 12.2 / 0 / 4 / 3 / 1 / WT / WT / Q61R / 3 / 3 / 0
599 / F / 56 / Yes / 10 / III / 11.8 / 0 / 2 / 6 / 0 / WT / WT / WT / NA / NA / NA
600 / F / 66 / Yes / 8 / II / 10.8 / 0 / 6 / 2 / 2 / WT / WT / WT / NA / NA / NA
601 / M / 50 / Yes / 8 / III / 10.6 / 0 / 2 / 2 / 1 / WT / WT / Q61K / 1 / 0 / 0
603 / F / 65 / Yes / 1.3 / II / 17.9 / 0 / 5 / 2 / 0 / WT / WT / WT / 3 / 1 / 0
604 / F / 46 / Yes / 7.5 / II / 14.9 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
605 / M / 61 / Yes / 15 / IV / 17.4 / 1 / 2 / 1 / 2 / WT / WT / WT / 2 / 0 / 3
606 / M / 60 / No / 2 / IV / 10.7 / 1 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
607 / M / 56 / Yes / 5 / II / 10.1 / 0 / 2 / 2 / 0 / WT / WT / WT / 3 / 0 / 1
608 / F / 49 / Yes / 0.1 / I / 10.1 / 0 / 2 / 4 / 2 / WT / WT / WT / NA / NA / NA
610 / M / 52 / No / 5 / III / 12 / 0 / 2 / 7 / 2 / WT / WT / G12C / NA / NA / NA
611 / M / 40 / Yes / 5 / III / 15.6 / 1 / 3 / 1 / 2 / WT / V600E / WT / NA / NA / NA
612 / F / 62 / Yes / 4 / III / 79 / 0 / 5 / 2 / 1 / WT / WT / WT / 2 / 0 / 1
613 / F / 47 / Yes / 1.2 / II / 41.6 / 1 / 2 / 8 / 0 / WT / WT / WT / NA / NA / NA
614 / M / 40 / Yes / 1.2 / II / 11 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
616 / M / 24 / No / 3 / II / 6 / 1 / 2 / 6 / 1 / WT / WT / Q61R / 2 / 2 / 0
617 / M / 63 / No / 3 / II / 10.6 / 0 / 2 / 3 / 2 / WT / WT / WT / NA / NA / NA
618 / F / 55 / Yes / 1.5 / II / 11.2 / 0 / 2 / 2 / 1 / WT / WT / WT / 3 / 3 / 1
619 / M / 44 / Yes / 5 / II / 11 / 0 / 9 / 4 / 1 / WT / WT / WT / 3 / 2 / 2
623 / F / 66 / Yes / 12 / III / 9.5 / 0 / 3 / 100 / 0 / WT / V600E / WT / NA / NA / NA
624 / F / 52 / Yes / 1 / I / 37.8 / 0 / 4 / 2 / 1 / WT / WT / Q61R / NA / NA / NA
626 / F / 74 / Yes / 7 / II / 9.4 / 0 / 2 / 1 / 1 / WT / WT / WT / 1 / 1 / 0
627 / M / 46 / Yes / 4 / II / 8.3 / 0 / 2 / 3 / 0 / WT / V600E / WT / NA / NA / NA
630 / M / 87 / Yes / 5 / III / 26.7 / 1 / 4 / 2 / 1 / WT / WT / WT / 3 / 0 / 0
631 / M / 18 / Yes / 2 / II / 9.9 / 0 / 2 / 2 / 1 / WT / WT / WT / 1 / 0 / 0
632 / F / 52 / Yes / 1.1 / II / 84.5 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
633 / M / 56 / Yes / 0.5 / I / 10.2 / 0 / 2 / 1 / 1 / WT / WT / Q61R / 1 / 1 / 1
634 / M / 48 / No / 3 / III / 17.6 / 0 / 2 / 2 / 1 / WT / WT / G12D / 1 / 0 / 0
635 / F / 81 / Yes / 3 / IV / 8.2 / 1 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
636 / M / 29 / No / 1.1 / I / 9.2 / 0 / 2 / 2 / 1 / WT / WT / WT / 3 / 1 / 0
637 / F / 46 / Yes / 2 / II / 14.6 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
638 / M / 77 / Yes / 3 / III / 15.6 / 1 / 4 / 5 / 0 / WT / WT / WT / 3 / 1 / 1
640 / M / 59 / Yes / 4.5 / II / 83 / 0 / 2 / 3 / 2 / WT / WT / WT / NA / NA / NA
641 / F / 54 / Yes / 5 / IV / 10 / 1 / 2 / 2 / 2 / WT / WT / Q61K / NA / NA / NA
642 / M / 47 / Yes / 8 / II / 12 / 0 / 3 / 27 / 2 / WT / WT / WT / NA / NA / NA
643 / M / 48 / No / 0.18 / I / 15.6 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
644 / M / 73 / Yes / 4 / II / 29.1 / 0 / 2 / 2 / 1 / WT / WT / WT / 3 / 2 / 1
645 / F / 25 / Yes / 2.5 / III / 17.2 / 1 / 4 / 10 / 2 / WT / WT / WT / NA / NA / NA
646 / M / 79 / Yes / 6 / II / 12.5 / 1 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
647 / M / 51 / Yes / 3 / III / 8.8 / 0 / 2 / 1 / 2 / WT / WT / WT / NA / NA / NA
649 / F / 61 / Yes / 6 / II / 7.7 / 0 / 15 / 2 / 2 / WT / WT / WT / NA / NA / NA
650 / F / 62 / No / 4 / II / 34 / 0 / 3 / 2 / 0 / WT / WT / WT / 3 / 0 / 1
651 / F / 51 / Yes / 40 / III / 9.2 / 1 / 2 / 2 / 2 / L576P / WT / WT / NA / NA / NA
652 / M / 62 / Yes / 4 / II / 9.6 / 0 / 3 / 9 / 2 / WT / WT / WT / NA / NA / NA
653 / M / 66 / No / 7 / III / 12.6 / 0 / 4 / 2 / 0 / WT / WT / WT / 1 / 0 / 0
654 / F / 89 / Yes / 10.5 / II / 5.8 / 0 / 2 / 1 / 2 / WT / WT / WT / NA / NA / NA
655 / F / 52 / Yes / 1.3 / II / 18.2 / 0 / 2 / 4 / 1 / WT / WT / WT / NA / NA / NA
656 / M / 44 / Yes / 1.3 / II / 11.6 / 0 / 2 / 2 / 1 / V560D / WT / WT / 3 / 0 / 0
657 / M / 67 / Yes / 3 / II / 11.6 / 0 / 2 / 2 / 1 / WT / WT / Q61R / NA / NA / NA
658 / M / 59 / Yes / 5 / III / 19.3 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
659 / M / 67 / Yes / 4 / II / 18.2 / 0 / 2 / 2 / 1 / WT / V600E / WT / 3 / 1 / 0
660 / F / 62 / Yes / 1.1 / I / 3.6 / 0 / 2 / 2 / 1 / WT / WT / Q61R / 3 / 0 / 2
661 / F / 58 / No / 2.9 / III / 26.7 / 1 / 2 / 2 / 1 / WT / V600E / WT / 2 / 1 / 2
662 / F / 37 / No / 2 / I / 3.7 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
663 / F / 30 / No / 2.3 / II / 6.2 / 0 / 2 / 2 / 1 / WT / WT / WT / 2 / 1 / 3
665 / F / 77 / Yes / 5 / II / 21.6 / 1 / 6 / 2 / 2 / WT / WT / WT / NA / NA / NA
666 / F / 73 / Yes / 1.5 / II / 16.7 / 0 / 2 / 3 / 2 / WT / WT / Q61R / NA / NA / NA
667 / F / 23 / Yes / 30 / II / 44.8 / 1 / 6 / 2 / 1 / WT / WT / Q61R / NA / NA / NA
668 / F / 75 / No / 0.9 / I / 6.3 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
669 / M / 31 / No / 5 / II / 6.6 / 0 / 8 / 2 / 1 / WT / WT / WT / NA / NA / NA
670 / M / 59 / Yes / 1.4 / III / 80.1 / 0 / 2 / 3 / 0 / WT / WT / WT / NA / NA / NA
672 / M / 44 / No / 9 / IV / 7.2 / 0 / 2 / 1 / 2 / WT / WT / WT / NA / NA / NA
673 / M / 50 / Yes / 3 / III / 5.6 / 0 / 2 / 2 / 0 / WT / WT / WT / 3 / 0 / 0
675 / M / 57 / No / 1.5 / I / 6.1 / 0 / 3 / 2 / 1 / WT / WT / WT / 1 / 0 / 0
676 / F / 63 / No / 3 / III / 27 / 0 / 2 / 2 / 1 / WT / WT / G12A / 1 / 0 / 0
679 / F / 53 / Yes / 3 / III / 11.4 / 0 / 4 / 2 / 2 / WT / WT / WT / NA / NA / NA
680 / M / 45 / Yes / 3 / II / 7.5 / 0 / 2 / 2 / 1 / WT / WT / Q61R / 2 / 0 / 0
683 / F / 67 / Yes / 10 / III / 6.7 / 0 / 3 / 1 / 0 / WT / WT / WT / NA / NA / NA
684 / M / 49 / Yes / 0.8 / I / 8.6 / 0 / 2 / 10 / 1 / WT / WT / WT / NA / NA / NA
685 / M / 41 / Yes / 4 / II / 34.8 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
686 / M / 63 / Yes / 4 / II / 34.6 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
687 / M / 58 / Yes / 3 / II / 62.4 / 1 / 4 / 2 / 1 / WT / WT / WT / 3 / 0 / 0
688 / F / 46 / Yes / 4 / III / 9.1 / 0 / 2 / 2 / 0 / WT / WT / WT / 2 / 0 / 0
689 / M / 39 / No / 2.4 / III / 29.3 / 0 / 2 / 2 / 1 / WT / WT / WT / 1 / 0 / 0
691 / F / 82 / No / 1 / I / 28.3 / 0 / 4 / 2 / 1 / WT / V600E / WT / NA / NA / NA
693 / F / 41 / Yes / 1.8 / II / 36.5 / 0 / 2 / 1 / 1 / WT / WT / WT / 2 / 0 / 0
694 / M / 53 / Yes / 3 / II / 36.9 / 0 / 2 / 9 / 1 / WT / WT / WT / NA / NA / NA
695 / M / 52 / Yes / 4 / IV / 5.1 / 1 / 2 / 2 / 0 / WT / WT / WT / NA / NA / NA
696 / F / 52 / Yes / 4 / II / 7.7 / 0 / 1 / 1 / 0 / WT / WT / WT / 0 / 0 / 0
698 / M / 64 / Yes / 2.2 / II / 8.9 / 0 / 2 / 34 / 0 / WT / WT / WT / NA / NA / NA
699 / F / 62 / Yes / 2 / II / 10.6 / 0 / 3 / 6 / 1 / WT / WT / WT / NA / NA / NA
700 / F / 55 / Yes / 2 / II / 84.3 / 0 / 2 / 1 / 2 / WT / WT / WT / NA / NA / NA
713 / M / 47 / Yes / 5 / II / 18 / 0 / 3 / 5 / 1 / WT / WT / WT / NA / NA / NA
714 / F / 43 / NA / 3.5 / III / 62 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
716 / F / 48 / No / 1.6 / I / 22 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
717 / F / 57 / No / 5 / III / 38 / 0 / 2 / 2 / 1 / D816Y / WT / WT / NA / NA / NA
718 / M / 58 / Yes / 1 / I / 54.2 / 0 / 2 / 2 / 2 / WT / WT / G15E / NA / NA / NA
720 / M / 45 / Yes / 5 / II / 64.4 / 0 / 2 / 1 / 1 / WT / WT / Q61R / NA / NA / NA
721 / M / 63 / Yes / 4.1 / III / 9.2 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
722 / M / 50 / Yes / 5 / II / 18.2 / 0 / 2 / 3 / 2 / WT / WT / WT / NA / NA / NA
723 / M / 65 / No / 7 / II / 9.8 / 1 / 2 / 2 / 1 / D816H / WT / WT / NA / NA / NA
724 / F / 38 / Yes / 4.4 / II / 17.4 / 0 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
726 / F / 39 / No / 8 / II / 16.7 / 0 / 3 / 3 / 2 / WT / WT / WT / NA / NA / NA
728 / M / 67 / No / 4 / II / 31.2 / 1 / 3 / 3 / 3 / L576P / WT / WT / NA / NA / NA
729 / F / 61 / Yes / 4 / II / 21 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
730 / M / 62 / No / 3 / II / 45.7 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
731 / M / 32 / Yes / 1.9 / II / 1.5 / 0 / 3 / 2 / 0 / WT / WT / WT / NA / NA / NA
734 / M / 55 / No / 7 / III / 21.2 / 0 / 4 / 7 / 2 / WT / WT / WT / NA / NA / NA
736 / M / 60 / Yes / 3 / III / 24 / 0 / 3 / 2 / 0 / WT / WT / Q61K / NA / NA / NA
738 / F / 52 / Yes / 4 / IV / 1 / 1 / 2 / 2 / 1 / WT / WT / G13V / NA / NA / NA
739 / M / 69 / Yes / 3 / II / 15 / 1 / 2 / 1 / 1 / WT / V600E / WT / NA / NA / NA
740 / F / 53 / No / 2 / I / 14.6 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
741 / M / 51 / No / 8 / II / 72.5 / 1 / 3 / 2 / 1 / WT / V600E / WT / NA / NA / NA
744 / F / 74 / Yes / 2 / IV / 63.7 / 1 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
745 / M / 62 / No / 10 / II / 14.3 / 0 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
746 / F / 58 / Yes / 9 / II / 27.3 / 1 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
748 / M / 55 / Yes / 11 / II / 36.6 / 1 / 3 / 3 / 2 / WT / WT / WT / NA / NA / NA
749 / F / 58 / Yes / 25 / II / 45.6 / 1 / 4 / 3 / 1 / WT / WT / WT / NA / NA / NA
750 / F / 52 / Yes / 4 / II / 12.3 / 0 / 2 / 2 / 1 / WT / V600E / NA / NA / NA / NA
752 / M / 59 / Yes / 2 / III / 18 / 0 / 12 / 3 / 2 / WT / WT / WT / NA / NA / NA
755 / M / 39 / NA / 3 / III / 12 / 1 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
757 / M / 56 / Yes / 2 / I / 17 / 0 / 3 / 2 / 2 / WT / V600E / WT / NA / NA / NA
758 / F / 25 / Yes / 1.2 / II / 14 / 0 / 5 / 2 / 2 / WT / WT / WT / NA / NA / NA
759 / F / 65 / Yes / 0.5 / I / 99 / 0 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
761 / M / 50 / Yes / 9 / IV / 15 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
763 / M / 57 / Yes / 1 / II / 15 / 0 / 22 / 5 / 2 / WT / WT / WT / NA / NA / NA
764 / F / 34 / Yes / NA / IV / 27 / 0 / 2 / 1 / 1 / WT / K601E / WT / NA / NA / NA
765 / F / 58 / Yes / 2 / II / 13 / 0 / 2 / 3 / 2 / WT / V600E / Q61R / NA / NA / NA
767 / F / 31 / Yes / 4 / III / 9 / 0 / 2 / 2 / 0 / WT / WT / WT / NA / NA / NA
769 / F / 92 / Yes / 5 / II / 41 / 0 / 2 / 3 / 1 / L576P / WT / G12C / NA / NA / NA
770 / M / 46 / NA / 4 / II / 14 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
776 / M / 65 / Yes / 5 / II / 10 / 0 / 4 / 8 / 1 / WT / WT / WT / NA / NA / NA
777 / F / 70 / Yes / 2 / II / 14 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
780 / F / 69 / Yes / 2 / III / 8 / 0 / 2 / 2 / 2 / WT / V600E / WT / NA / NA / NA
781 / M / 58 / Yes / 2 / I / 10 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
782 / F / 43 / Yes / 8 / IV / 16 / 1 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
786 / M / 47 / Yes / 8 / IV / 18 / 1 / 8 / 2 / 2 / WT / V600E / WT / NA / NA / NA
787 / F / 56 / No / 15 / II / 8 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
788 / M / 49 / Yes / 6 / II / 8 / 0 / 2 / 2 / 2 / WT / V600E / WT / NA / NA / NA
789 / M / 85 / Yes / 5.5 / IV / 8 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
790 / F / 60 / Yes / 5 / II / 8 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
791 / F / 33 / Yes / 2 / III / 19 / 0 / 2 / 2 / 2 / WT / WT / Q61R / NA / NA / NA
792 / F / 42 / No / 2.8 / II / 12 / 0 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
794 / M / 59 / Yes / 2 / IV / 36 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
795 / F / 60 / No / 3 / II / 20 / 0 / 2 / 3 / 2 / WT / WT / Q61R / NA / NA / NA
798 / M / 65 / NA / 3 / IV / 101 / 0 / 2 / 2 / 1 / WT / WT / Q61R / NA / NA / NA
799 / F / 87 / Yes / 1 / IV / 28 / 0 / 3 / 2 / 2 / WT / WT / WT / NA / NA / NA
800 / F / 49 / Yes / 1 / III / 32 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
801 / M / 69 / No / 6 / III / 24 / 0 / 2 / 2 / 1 / WT / V600E / WT / NA / NA / NA
803 / M / 51 / Yes / NA / III / 9 / 1 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
804 / M / 40 / NA / NA / I / 101 / 0 / 2 / 2 / 2 / WT / WT / Q61L / NA / NA / NA
805 / F / 36 / Yes / 2 / II / 6 / 0 / 2 / 10 / 2 / WT / WT / WT / NA / NA / NA
807 / M / 78 / No / 1.3 / III / 37 / 0 / 9 / 2 / 1 / WT / WT / WT / NA / NA / NA
809 / M / 44 / Yes / 1 / I / 17 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
814 / M / 44 / NA / 4 / IV / 46 / 0 / 2 / 9 / 1 / WT / V600E / WT / NA / NA / NA
816 / M / 49 / Yes / 6 / II / 6 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
819 / F / 50 / No / 2 / I / 23 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
820 / F / 55 / No / 4 / III / 9 / 0 / 3 / 7 / 0 / WT / WT / WT / NA / NA / NA
823 / F / 53 / NA / NA / IV / 39 / 1 / 2 / 2 / 1 / WT / WT / Q61K / NA / NA / NA
826 / F / 49 / Yes / NA / III / 20 / 0 / 2 / 18 / 2 / V560D / WT / WT / NA / NA / NA
829 / M / 32 / No / 1 / I / 17 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
831 / M / 50 / Yes / 19.5 / III / 22 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
832 / F / 42 / No / 4 / IV / 11 / 1 / 2 / 3 / 1 / WT / WT / Q61H / NA / NA / NA
834 / M / 24 / Yes / 1.2 / II / 20 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
835 / M / 37 / Yes / 2.5 / II / 21 / 0 / 3 / 1 / 1 / WT / WT / WT / NA / NA / NA
836 / M / 42 / Yes / 5 / III / 1 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
844 / F / 40 / Yes / 3 / III / 37 / 0 / 2 / 1 / 1 / WT / WT / WT / NA / NA / NA
892 / F / 36 / No / 4 / III / 9 / 0 / 3 / 2 / 1 / WT / V600E / WT / NA / NA / NA
894 / F / 45 / Yes / 2 / II / 7 / 0 / 2 / 18 / 2 / WT / V600E / WT / NA / NA / NA
895 / F / 53 / Yes / 3.5 / III / 87 / 0 / 2 / 2 / 1 / WT / WT / WT / NA / NA / NA
941 / M / 54 / Yes / NA / IV / 45 / 0 / 3 / 3 / 2 / NA / NA / NA / NA / NA / NA
942 / M / 60 / Yes / 5 / IV / 42 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
943 / F / 45 / Yes / 5 / IV / 8 / 0 / 2 / 2 / 2 / D816H / WT / WT / NA / NA / NA
944 / F / 40 / No / 4.4 / IV / 27 / 0 / 17 / 2 / 2 / WT / WT / WT / NA / NA / NA
945 / M / 54 / Yes / NA / IV / 29 / 0 / 6 / 2 / 2 / WT / WT / WT / NA / NA / NA
946 / M / 64 / Yes / 2.7 / IV / 19 / 0 / 2 / 10 / 2 / D820Y / WT / WT / NA / NA / NA
947 / F / 48 / Yes / 1.5 / IV / 35 / 0 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
948 / F / 69 / No / 2 / I / 3 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
949 / M / 28 / Yes / 2.5 / IV / 35 / 0 / 2 / 5 / 1 / WT / WT / WT / NA / NA / NA
950 / F / 62 / No / NA / IV / 7 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
951 / M / 56 / No / 0.1 / III / 6 / 0 / 2 / 2 / 2 / WT / WT / WT / NA / NA / NA
952 / M / 75 / Yes / NA / III / 8 / 0 / 2 / 4 / 2 / NA / NA / NA / NA / NA / NA
953 / M / 83 / Yes / 4 / IV / 6 / 0 / 2 / 4 / 2 / NA / NA / NA / NA / NA / NA
954 / M / 60 / No / NA / IV / 7 / 0 / 2 / 2 / 0 / NA / NA / NA / NA / NA / NA
955 / M / 56 / Yes / 9 / III / 9 / 0 / 2 / 5 / 2 / NA / NA / NA / NA / NA / NA
956 / M / 53 / Yes / 3 / IV / 10 / 0 / 3 / 2 / 1 / WT / WT / WT / NA / NA / NA
957 / M / 49 / Yes / NA / III / 16 / 0 / 43 / 2 / 2 / WT / WT / G12D / NA / NA / NA
Abbreviations: F, female; M, male; NA, not available; OS, overall survival; WT, wild type.
a “1” indicates survival, and “0” indicates for death.
b The copy number variations (CNV) detected by QuantiGenePlex DNA assay were shown.
c The amino acid aberration but not the nucleotide change was listed.The hotspot regions (exons 9, 11, 13, 17 and 18 of Kit gene, exons 11 and 15 of Braf gene, and exons 1 and 2 of Nras gene) of Kit, Braf and Nras were examined for mutations by PCR amplification of DNA followed by DNA sequencing (16, 17).
dThe IHC staining score for each sample, counting the intensity and density of the staining, was graded as 0, 1, 2, and 3 (“0” as negative, and “3” as the strongest; or “0” as negative, and “1”, “2” and “3” as positive).
1
SupplementaryTable S4. Validation of copy number variations of genes related to CDK4 pathway by Q-PCR and mutation status of therapeutic targets
CDK4 aberration / CNV statusa / Genetic mutation of therapeutic targets% (positive cases/examined cases)b
% (positive cases/examined cases) / Kit / Braf / Nras
Cdk4 gain / 42.9 (183/427) / 9.5 (40/421) / 13.6 (57/420) / 14.5 (56/385)
Ccnd1 gain / 26.2 (112/427) / 9.3 (39/421) / 12.6 (53/420) / 15.1 (59/391)
P16INK4a loss / 52.1 (212/407) / 9.7 (39/401) / 12.8 (51/400) / 15.1 (56/370)
Abbreviations: CNV, copy number variation.
a Only a major proportion of the samples were validated for CNVs by Q-PCR.
b The hotspot regions (exons 9, 11, 13, 17 and 18 of Kit gene, exons 11 and 15 of Braf gene, and exons 1 and 2 of Nras gene) of Kit, Braf and Nras were examined for mutations by PCR amplification of DNA followed by DNA sequencing (16, 17).
1
Supplementary Table S5. Correlation between copy number variations and protein expression of CDK4 pathway in acral melanoma
Genes / CNV status / IHC score % (assigned cases/examined cases) / P valuea0 / 1 / 2 / 3
Cdk4 / Normal / 11/76 (14.5) / 25/76 (32.9) / 22/76(28.9) / 18/76 (23.7) / 0.018
Gain / 0/37(0.0) / 11/37(29.7) / 14/37(37.8) / 12/37(32.4)
P16INK4a / Normal / 0/4(0.0) / 0/4(0.0) / 3/4(75.0) / 1/4(25.0) / 0.000
Loss / 71/109(65.1) / 29/109(26.6) / 7/109(6.4) / 2/109(1.8)
Ccnd1 / Normal / 44/77(57.1) / 18/77(23.4) / 10/77(13.0) / 5/77 (6.5) / 0.002
Gain / 0/11 (0.0) / 3/11(27.3) / 7/11(63.6) / 1/11(9.1)
Loss / 13/25(52.0) / 6/25(24.0) / 5/25(20.0) / 1/25(4.0)
a For evaluation of the correlation between CDK4 pathway aberrations and protein expression, the chi-square tests were used.
SupplementaryTable S6. Correlation of concurrent CDK4 pathway aberrations to clinicopathologic features of acral melanoma
Clinicopathologic factor / Cdk4 gain plus Ccnd1 gain / Cdk4 gainplus P16INK4a lossPositive / Negative / P valuea / Positive / Negative / P valuea
Age (year) / 0.427 / 0.049
Median (range) / 55.9±11.7 / 54.5±13.9 / 56.9±13.7 / 54.1±13.6
Gender n (%) / 0.121 / 0.946
Male / 47 (64.4) / 241(54.6) / 67(56.3) / 221(55.9)
Female / 26 (35.6) / 200(45.4) / 52(43.7) / 174(44.1)
Ulceration n (%) / 0.593 / 0.271
Yes / 51 (70.8) / 319(73.8) / 82(69.5) / 288(74.6)
No / 21 (29.2) / 113(26.2) / 36(30.5) / 98(25.4)
Thickness (mm) / < 0.001 / < 0.001
Median (range) / 5.0 (0.5,25.0) / 3.0(0.1,40.0) / 5.0(0.5,30.0) / 3.0(0.1,40.0)
Stages n (%) / 0.373 / 0.607
I / 7 (9.6) / 47(10.7) / 9(7.6) / 45(11.4)
II / 39 (53.4) / 210(47.6) / 60 (50.4) / 189(47.8)
III / 22 (30.1) / 121(27.4) / 35 (29.4) / 108(27.3)
IV / 5 (6.8) / 63(14.3) / 15 (12.6) / 53(13.4)
Survival (months) / 0.743 / 0.005
Median (95% CI) / 45.6 (31.7, 59.5) / 48.6(39.7,57.5) / 40.0(32.3,47.7) / 59.1(49.1,69.1)
Supplementary Table S6 (continued)
Clinicopathologic factor / Cdk4 gain plus Ccnd1 loss / Cdk4 gain, P16INK4a loss and Ccnd1 gain
Positive / Negative / P valuea / Positive / Negative / P valuea
Age (year) / 0.872 / 0.119
Median (range) / 55.2±12.8 / 54.7±13.7 / 57.8±11.7 / 54.4±13.8
Gender n (%) / 0.513 / 0.669
Male / 15(62.5) / 273(55.7) / 26(59.1) / 262(55.7)
Female / 9(37.5) / 217(44.3) / 18(40.9) / 208(44.3)
Ulceration n (%) / 0.206 / 0.354
Yes / 20(87.0) / 350(72.8) / 29(67.4) / 341(74.0)
No / 3(13.0) / 131(27.2) / 14(32.6) / 120(26.0)
Thickness (mm) / 0.008 / 0.005
Median (range) / 6.2(0.2,14.0) / 3.5(0.1,40.0) / 5.0 (1.0,25.0) / 3.5(0.1,40.0)
Stages n (%) / 0.537 / 0.638
I / 0(0.0) / 54(11.0) / 4(9.1) / 50(10.6)
II / 15(62.5) / 234(47.8) / 23(52.3) / 226(48.1)
III / 4(16.7) / 139(28.4) / 14(31.8) / 129(27.4)
IV / 5(20.8) / 63(12.9) / 3(6.8) / 65(13.8)
Survival (months) / 0.007 / 0.129
Median (95% CI) / 33.0(29.1,36.9) / 48.6(40.2,57.0) / 36.0(28.4,43.6) / 53.6(44.8,62.4)
Supplementary Table S6 (continued)
Clinicopathologic factor / Cdk4 gain, P16INK4a loss and Ccnd1 loss / P16INK4a loss plus Ccnd1 gain
Positive / Negative / P valuea / Positive / Negative / P valuea
Age (year) / 0.362 / 0.509
Median (range) / 57.6±12.2 / 54.6±13.7 / 55.7±12.7 / 54.6±13.8
Gender n (%) / 0.967 / 0.088
Male / 10(55.6) / 278(56.0) / 50(64.9) / 238(54.5)
Female / 8(44.4) / 218(44.0) / 27(35.1) / 199(45.5)
Ulceration n (%) / 0.214 / 0.250
Yes / 16(88.9) / 354(72.8) / 51(68.0) / 319(74.4)
No / 2(11.1) / 132(27.2) / 24(32.0) / 110(25.6)
Thickness (mm) / 0.017 / 0.096
Median (range) / 6.5(1.3,14.0) / 3.6(0.1,40.0) / 4.0 (0.8,25.0) / 3.5(0.1,40.0)
Stages n (%) / 0.890 / 0.677
I / 0(0.0) / 54(10.9) / 6(7.8) / 48(11.0)
II / 12(66.7) / 237(47.8) / 38(49.4) / 211(48.3)
III / 3(16.7) / 140(28.2) / 24(31.2) / 119(27.2)
IV / 3(16.7) / 65(13.1) / 9(11.7) / 59(13.5)
Survival (months) / 0.080 / 0.674
Median (95% CI) / 33.0(29.2,36.8) / 47.0(39.0,55.0) / 43.6(35.5,51.7) / 53.6(44.2,63.0)
Supplementary Table S6 (continued)
Clinicopathologic factor / P16INK4a loss plus Ccnd1 loss
Positive / Negative / P valuea
Age (year) / 0.796
Median (range) / 54.3±12.6 / 54.8±13.8
Gender n (%) / 0.635
Male / 33(53.2) / 255(56.4)
Female / 29(46.8) / 197(43.6)
Ulceration n (%) / 0.009
Yes / 54(87.1) / 316(71.5)
No / 8(12.9) / 126(28.5)
Thickness (mm) / 0.336
Median (range) / 4.0 (0.5,14.0) / 4.0 (0.1,40.0)
Stages n (%) / 0.894
I / 3(4.8) / 51(11.3)
II / 36(58.1) / 189 (51.6)
III / 14(22.6) / 102 (27.9)
IV / 9(14.5) / 33 (9.0)
Survival (months) / 0.588
Median (95% CI) / 45.8(25.2,66.4) / 44.8 (41.4, 55.8)
a For evaluation of age, the two independent sample t-test were used. For evaluation of gender, ulceration and stages, the chi-square tests or Fisher's exact tests were used.For evaluation of thickness, Mann-Whitney U tests were used. For evaluation of OS time, Log-Rank tests were used.
Supplementary Table S7. Univariate and multivariate analysis of risk factors associated with overall survival
Clinicopathologic factor / Univariate risk ratio (95% CI) / P value / Multivariate risk ratio (95% CI) / P valueAge (> 60) / 0.216 (0.147-0.319) / 0.001 / 2.470 (1.730-3.528) / 0.001
Gender / 0.919 (0.636-1.327) / 0.651
Ulceration / 0.156 (0.115-0.212) / 0.001 / 0.212 (0.161-0.280) / 0.001
Thickness (> 4 mm) / 0.968 (0.740-1.267) / 0.814
Stages / 0.001 / 1.270 (1.072-1.505) / 0.006
Cdk4 gain / 1.389 (1.041-1.886) / 0.027
Ccnd1 gain / 1.311 (0.938-1.803) / 0.121
P16INK4a loss / 1.494 (1.077-1.980) / 0.015
Cdk4 gain + Ccnd1 gain / 1.068 (0.713-1.609) / 0.743
Cdk4 gain + P16INK4a loss / 1.542 (1.159-2.260) / 0.005
Ccnd1 gain + P16INK4a loss / 1.085 (0.735-1.613) / 0.674
Cdk4 gain + Ccnd1 gain + P16INK4a loss / 1.396 (0.899-2.435) / 0.129
≥1 CNVs / 1.405 (0.899-2.043) / 0.148
Abbreviations: CNV, copy number variation.
Supplementary Table S8. Correlation of concurrent CDK4 pathway aberrations to mitotic rate and TILs score of acral melanoma
CNV status / Mitotic rate n (%)a / TILs score n (%)b≤ 4 / > 4 / P valuec / 1 / 2 / 3 / P valuec
p16INK4a / 0.350 / 0.315
Normal / 26 (54.2) / 20 (33.9) / 24 (51.1) / 13 (38.2) / 9 (34.6)
Loss / 22 (45.8) / 39 (66.1) / 23 (48.9) / 21 (61.8) / 17 (65.4)
Ccnd1 / 0.505 / 0.912
Normal / 32 (66.7) / 33 (55.9) / 29 (61.7) / 21 (61.8) / 15 (57.7)
Gain / 11 (22.9) / 19 (32.2) / 12 (25.5) / 9 (26.5) / 9 (34.6)
Loss / 5 (10.4) / 7 (11.9) / 6 (12.8) / 4 (11.8) / 2 (7.7)
Cdk4 / 0.059 / 0.552
Normal / 29 (60.4) / 37 (62.7) / 29 (61.7) / 23 (67.6) / 14 (53.8)
Gain / 19 (39.6) / 22 (37.3) / 18 (38.3) / 11 (32.4) / 12 (46.2)
Cdk4 gain plus Ccnd1 gain / 0.704 / 0.856
Positive / 6 (12.5) / 6 (10.2) / 6 (12.8) / 3 (8.8) / 3 (11.5)
Negative / 42 (87.5) / 53 (89.8) / 41 (87.2) / 31 (91.2) / 23 (88.5)
Cdk4 gain plus P16INK4a loss / 0.451 / 0.369
Positive / 10 (20.8) / 16 (27.1) / 10 (21.3) / 7 (20.6) / 9 (34.6)
Negative / 38 (79.2) / 43 (72.9) / 37 (78.7) / 27 (79.4) / 17 (65.4)
Cdk4 gain plus Ccnd1 loss / 1.000 / 0.572
Positive / 1 (2.1) / 2 (3.4) / 2 (4.3) / 1 (2.9) / 0 (0.0)
Negative / 47 (97.9) / 57 (96.6) / 45 (95.7) / 33 (97.1) / 26 (100)
P16INK4a loss plus Ccnd1 gain / 0.461 / 0.915
Positive / 5 (10.4) / 9 (15.3) / 6 (12.8) / 4 (11.8) / 4 (15.4)
Negative / 43 (89.6) / 50 (84.7) / 41 (87.2) / 30 (88.2) / 22 (84.6)
P16INK4a loss plus Ccnd1 loss / 0.282 / 0.682
Positive / 2 (4.2) / 7 (11.9) / 3 (6.4) / 4 (11.8) / 2 (7.7)
Negative / 46 (95.8) / 52 (88.1) / 44 (93.6) / 30 (88.2) / 24 (92.3)
Cdk4 gain, P16INK4a loss and Ccnd1 gain / 1.000 / 0.677
Positive / 2 (4.2) / 3 (5.1) / 2 (4.3) / 1 (2.9) / 2 (7.7)
Negative / 46 (95.8) / 56 (94.9) / 45 (95.7) / 33 (97.1) / 24 (92.3)
Cdk4 gain, P16INK4a loss and Ccnd1 loss / 0.648 / 0.572
Positive / 1 (2.1) / 2 (3.4) / 2 (4.3) / 1 (2.9) / 0 (0.0)
Negative / 47 (97.9) / 57 (96.6) / 45 (95.7) / 33 (97.1) / 26 (100)
Abbreviations: CNV, copy number variation; TILs: Tumor-Infiltrating Lymphocytes
a For mitotic rate, the highest mitotic count per 10 high-power fields of three separate counts was recorded.
b For tumor-infiltrating lymphocytes, an estimate of the total area of invasive lymphocytes as a proportion of the overall tissue section was made and graded as follows: lymphocytes with < 25% of invasive growth scored 1, moderate (25-75%) invasive growth scored 2,and extensive invasive growth (>75%) scored 3.
cFor evaluation of mitotic rate and TILs, the chi-square tests were used.
1