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Supplemental data

Table S1: Results of Spearman Correlation Test between different ALK FISH probe (Dako vs Abbott) (n=33).

r p probe mean st. dev. median min max

ALK_R 0.60 0.0002 Dako 0.077 0.156 0.040 0.000 0.886

Abbott 0.081 0.176 0.037 0.000 0.969

ALK_S 0.38 0.0305 Dako 0.031 0.032 0.022 0.000 1.136

Abbott 0.029 0.028 0.024 0.000 1.153

ALK_L 0.51 0.0023 Dako 0.029 0.118 0.002 0.000 0.682

Abbott 0.038 0.163 0.000 0.000 0.939

ALK_FA -0.05 0.7576 Dako 0.003 0.013 0.000 0.000 0.682

Abbott 0.000 0.000 0.000 0.000 0.004

ALK_D 0.11 0.5082 Dako 0.013 0.035 0.000 0.000 0.194

Abbott 0.014 0.055 0.003 0.000 0.322

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D) ALK_S: ALK positive cells with short split

ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern

(2)

Supplemental data

ALK Dako probe ALK Abbott probe

1% 0%

2% 0%

25% 40%

4% 3%

5% 5%

89% 97%

6% 10%

4% 2%

3% 1%

6% 5%

4% 2%

2% 0%

5% 5%

2% 4%

0% 2%

2% 1%

9% 8%

8% 12%

4% 0%

4% 4%

26% 23%

3% 5%

0% 3%

5% 9%

2% 4%

2% 4%

2% 4%

3% 3%

2% 5%

7% 1%

5% 6%

9% 2%

6% 2%

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D)

Figure S1: Rate of ALK_R cells detected by ALK Dako and ALK Abbott probes on lung ADC specimens hibridized with both probes (n=33).

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

ALK Dako probe

ALK Abbott probe

(3)

Supplemental data

Table S2: Results of Spearman Correlation Test among three operators (A, B, C)

operator operator operator

r p r p r p operator mean st. dev. median min max

ALK_R 0.87 0.3333 0.87 0.3333 1.00 <0.0001 A 0.058 0.017 0.048 0.048 0.078

B 0.062 0.015 0.067 0.046 0.075

C 0.053 0.018 0.045 0.040 0.075

ALK_S 0.50 0.6667 0.50 0.6667 1.00 <0.0001 A 0.039 0.009 0.041 0.029 0.046

B 0.033 0.010 0.031 0.024 0.044

C 0.031 0.008 0.028 0.023 0.039

ALK_L -1.00 <0.0001 1.00 <0.0001 -1.00 <0.0001 A 0.011 0.007 0.009 0.005 0.018

B 0.014 0.003 0.013 0.012 0.017

C 0.013 0.006 0.010 0.010 0.019

ALK_FA 1.00 <0.0001 0.87 0.3333 0.87 0.3300 A 0.003 0.003 0.002 0.000 0.000

B 0.004 0.000 0.004 0.000 0.006

C 0.000 0.000 0.000 0.000 0.002

ALK_D 1.00 <0.0001 0.50 0.6670 0.50 0.6670 A 0.006 0.003 0.008 0.002 0.008

B 0.112 0.009 0.014 0.002 0.018

C 0.009 0.005 0.006 0.006 0.015

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D) ALK_S: ALK positive cells with short split

ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern

A vs B A vs C B vs C

(4)

Supplemental data

operator A operator B operator C

totali su v1 4.8% 4.6% 4.0%

totale su v2 7.8% 7.5% 7.5%

totale su v3 4.8% 6.7% 4.5%

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D) ALK_S: ALK positive cells with short split

ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern

Figure S2: Rate of ALK_R cells detected by 3 operators (A, B and C) on 3 ALK negative controls (>1700 nuclei)

0%

2%

4%

6%

8%

10%

12%

14%

operator A

operator B operator C

(5)

Supplemental data

Table S3: Raw data of ALK FISH patterns on the entire cohort of lung ADC patients (n=232)

# case # cells scored ALK_R ALK_S ALK_L ALK_FA ALK_D

1 200 0.0% 0.0% 0.0% 0.0% 0.0%

2 100 0.0% 0.0% 0.0% 0.0% 0.0%

3 120 0.0% 0.0% 0.0% 0.0% 0.0%

4 616 0.0% 0.0% 0.0% 0.0% 0.0%

5 58 65.5% 0.0% 0.0% 0.0% 65.5%

6 276 0.7% 0.0% 0.7% 0.0% 0.0%

7 122 4.9% 0.0% 3.3% 0.0% 1.6%

8 600 0.5% 0.0% 0.5% 0.0% 0.0%

9 336 1.2% 0.0% 1.2% 0.0% 0.0%

10 100 29.0% 0.0% 3.0% 0.0% 26.0%

11 160 3.1% 0.0% 2.5% 0.6% 0.0%

12 309 1.0% 0.0% 0.6% 0.0% 0.3%

13 187 10.2% 3.7% 4.8% 0.5% 1.1%

14 208 4.8% 2.4% 1.0% 0.0% 1.4%

15 58 93.1% 5.2% 86.2% 1.7% 0.0%

16 500 2.2% 0.6% 0.4% 0.0% 1.2%

17 200 3.5% 3.5% 0.0% 0.0% 0.0%

18 300 4.0% 2.0% 0.3% 0.0% 1.7%

19 200 0.5% 0.5% 0.0% 0.0% 0.0%

20 463 0.2% 0.2% 0.0% 0.0% 0.0%

21 436 1.6% 0.9% 0.7% 0.0% 0.0%

22 89 88.8% 0.0% 5.6% 0.0% 83.1%

23 420 9.3% 1.9% 5.0% 1.0% 1.4%

24 180 3.3% 2.8% 0.0% 0.0% 0.6%

25 311 0.6% 0.0% 0.6% 0.0% 0.0%

26 200 1.0% 1.0% 0.0% 0.0% 0.0%

27 472 3.8% 0.0% 2.8% 0.2% 0.8%

28 298 0.3% 0.0% 0.3% 0.0% 0.0%

29 500 1.2% 0.0% 1.0% 0.0% 0.2%

30 352 1.1% 0.0% 1.1% 0.0% 0.0%

31 447 1.3% 0.4% 0.9% 0.0% 0.0%

32 375 26.7% 13.9% 8.3% 1.6% 2.9%

33 329 4.6% 0.3% 3.0% 0.0% 1.2%

34 664 0.8% 0.0% 0.6% 0.0% 0.2%

35 282 10.6% 8.2% 1.4% 0.7% 0.4%

36 70 0.0% 0.0% 0.0% 0.0% 0.0%

37 422 4.5% 2.8% 0.7% 0.5% 0.5%

38 950 2.3% 1.3% 0.7% 0.1% 0.2%

39 372 0.5% 0.5% 0.0% 0.0% 0.0%

40 300 20.7% 18.0% 2.7% 0.0% 0.0%

41 434 5.3% 3.7% 0.7% 0.0% 0.9%

42 400 2.5% 2.0% 0.3% 0.0% 0.3%

43 896 7.8% 4.6% 2.2% 0.0% 1.0%

44 420 4.5% 3.1% 0.7% 0.0% 0.7%

45 130 2.3% 1.5% 0.8% 0.0% 0.0%

46 406 1.5% 0.7% 0.5% 0.0% 0.2%

47 128 4.7% 3.1% 0.0% 0.0% 1.6%

48 209 3.8% 3.3% 0.0% 0.0% 0.5%

49 220 0.9% 0.0% 0.0% 0.0% 0.9%

50 376 3.7% 2.9% 0.5% 0.0% 0.3%

51 205 2.4% 2.0% 0.0% 0.0% 0.5%

52 147 1.4% 0.7% 0.0% 0.0% 0.7%

53 184 3.8% 2.7% 0.0% 0.0% 1.1%

54 137 2.2% 0.0% 0.7% 0.0% 1.5%

55 309 2.9% 2.3% 0.6% 0.0% 0.0%

56 85 44.7% 0.0% 1.2% 0.0% 43.5%

57 102 4.9% 2.0% 0.0% 2.0% 1.0%

(6)

58 173 1.2% 0.6% 0.0% 0.0% 0.6%

59 132 10.6% 10.6% 0.0% 0.0% 0.0%

60 240 2.9% 2.5% 0.4% 0.0% 0.0%

61 100 23.0% 23.0% 0.0% 0.0% 0.0%

62 148 20.9% 19.6% 0.7% 0.7% 0.0%

63 78 6.4% 2.6% 0.0% 0.0% 3.8%

64 710 3.1% 2.3% 0.7% 0.1% 0.0%

65 252 1.2% 1.2% 0.0% 0.0% 0.0%

66 395 9.1% 8.1% 1.0% 0.0% 0.0%

67 400 3.3% 3.3% 0.0% 0.0% 0.0%

68 400 9.5% 8.5% 1.0% 0.0% 0.0%

69 127 68.5% 11.0% 6.3% 5.5% 45.7%

70 372 5.6% 2.2% 0.5% 0.3% 2.7%

71 509 5.7% 5.7% 0.0% 0.0% 0.0%

72 369 10.3% 5.7% 4.1% 0.0% 0.5%

73 544 8.8% 4.4% 2.6% 0.9% 0.9%

74 621 4.3% 3.1% 1.1% 0.0% 0.2%

75 402 2.2% 1.5% 0.5% 0.0% 0.2%

76 333 9.0% 4.8% 3.9% 0.3% 0.0%

77 571 4.2% 3.2% 0.7% 0.0% 0.4%

78 412 3.4% 2.7% 0.2% 0.0% 0.5%

79 313 4.2% 1.9% 1.0% 0.3% 1.0%

80 621 9.7% 6.1% 1.4% 0.0% 2.1%

81 100 100.0% 0.0% 0.0% 0.0% 100.0%

82 364 8.5% 5.8% 1.4% 0.0% 1.4%

83 447 6.3% 4.0% 1.3% 0.0% 0.9%

84 210 4.8% 3.8% 0.5% 0.0% 0.5%

85 400 1.8% 1.3% 0.5% 0.0% 0.0%

86 183 1.6% 1.1% 0.0% 0.0% 0.5%

87 209 4.3% 3.3% 0.5% 0.0% 0.5%

88 365 5.5% 4.4% 0.5% 0.0% 0.5%

89 368 4.9% 4.3% 0.5% 0.0% 0.0%

90 210 5.2% 4.8% 0.5% 0.0% 0.0%

91 487 3.9% 3.3% 0.2% 0.0% 0.4%

92 239 10.0% 7.9% 2.1% 0.0% 0.0%

93 413 13.6% 13.6% 0.0% 0.0% 0.0%

94 299 1.7% 1.7% 0.0% 0.0% 0.0%

95 255 0.8% 0.4% 0.0% 0.0% 0.4%

96 184 6.5% 5.4% 0.0% 0.0% 1.1%

97 279 12.5% 8.6% 3.9% 0.0% 0.0%

98 100 5.0% 5.0% 0.0% 0.0% 0.0%

99 113 4.4% 4.4% 0.0% 0.0% 0.0%

100 533 12.9% 12.9% 0.0% 0.0% 0.0%

101 222 5.9% 1.4% 0.9% 0.0% 3.6%

102 343 8.5% 6.4% 0.6% 0.0% 1.5%

103 310 1.9% 0.3% 0.0% 0.0% 1.6%

104 312 25.6% 21.8% 2.2% 0.3% 1.3%

105 529 7.2% 5.7% 0.9% 0.2% 0.4%

106 100 85.0% 0.0% 4.0% 0.0% 81.0%

107 293 8.2% 7.8% 0.3% 0.0% 0.0%

108 405 9.4% 6.9% 1.2% 0.0% 1.2%

109 92 10.9% 10.9% 0.0% 0.0% 0.0%

110 64 95.3% 15.6% 75.0% 0.0% 4.7%

111 113 1.8% 0.0% 0.0% 0.0% 1.8%

112 109 6.4% 4.6% 0.0% 0.0% 1.8%

113 149 6.7% 4.7% 1.3% 0.0% 0.7%

114 100 0.0% 0.0% 0.0% 0.0% 0.0%

115 101 1.0% 1.0% 0.0% 0.0% 0.0%

116 109 5.5% 5.5% 0.0% 0.0% 0.0%

117 100 10.0% 7.0% 0.0% 0.0% 3.0%

118 110 10.0% 0.9% 6.4% 0.0% 2.7%

119 100 3.0% 3.0% 0.0% 0.0% 0.0%

(7)

120 105 0.0% 0.0% 0.0% 0.0% 0.0%

121 102 98.0% 0.0% 0.0% 0.0% 98.0%

122 105 1.0% 1.0% 0.0% 0.0% 0.0%

123 86 9.3% 9.3% 0.0% 0.0% 0.0%

124 102 8.8% 6.9% 2.0% 0.0% 0.0%

125 100 7.0% 6.0% 1.0% 0.0% 0.0%

126 101 2.0% 2.0% 0.0% 0.0% 0.0%

127 102 7.8% 3.9% 2.0% 0.0% 2.0%

128 103 3.9% 3.9% 0.0% 0.0% 0.0%

129 101 3.0% 3.0% 0.0% 0.0% 0.0%

130 203 1.0% 0.5% 0.0% 0.5% 0.0%

131 422 4.0% 3.3% 0.2% 0.0% 0.5%

132 257 2.7% 2.7% 0.0% 0.0% 0.0%

133 311 3.2% 2.9% 0.0% 0.0% 0.3%

134 321 4.0% 3.7% 0.3% 0.0% 0.0%

135 342 5.8% 4.7% 0.6% 0.3% 0.3%

136 320 6.3% 5.9% 0.3% 0.0% 0.0%

137 618 2.1% 1.5% 0.3% 0.0% 0.3%

138 86 88.4% 0.0% 0.0% 87.2% 1.2%

139 310 1.0% 0.6% 0.3% 0.0% 0.0%

140 300 0.0% 0.0% 0.0% 0.0% 0.0%

141 433 5.1% 2.5% 1.4% 0.2% 0.9%

142 350 31.4% 2.6% 4.0% 0.0% 24.9%

143 202 15.8% 0.0% 13.9% 0.0% 2.0%

144 228 3.5% 0.0% 3.5% 0.0% 0.0%

145 305 15.0% 0.0% 9.0% 0.0% 6.0%

146 1186 3.7% 0.0% 3.1% 0.0% 0.6%

147 389 4.9% 0.0% 3.6% 0.0% 1.3%

148 77 92.2% 7.8% 79.2% 3.9% 1.3%

149 528 6.8% 4.9% 1.3% 0.0% 0.6%

150 1304 3.3% 2.3% 0.2% 0.0% 0.8%

151 1323 2.0% 1.3% 0.2% 0.0% 0.5%

152 956 5.6% 3.6% 0.1% 0.0% 2.0%

153 209 1.9% 1.4% 0.5% 0.0% 0.0%

154 236 9.3% 5.1% 0.8% 0.0% 3.4%

155 112 7.1% 6.3% 0.0% 0.0% 0.9%

156 313 3.2% 2.6% 0.0% 0.0% 0.6%

157 308 1.3% 1.3% 0.0% 0.0% 0.0%

158 222 5.0% 4.5% 0.0% 0.0% 0.5%

159 375 2.9% 2.4% 0.0% 0.0% 0.5%

160 191 0.5% 0.5% 0.0% 0.0% 0.0%

161 72 5.6% 4.2% 0.0% 0.0% 1.4%

162 270 1.1% 1.1% 0.0% 0.0% 0.0%

163 258 8.5% 6.6% 0.8% 0.0% 1.2%

164 103 8.7% 4.9% 1.0% 0.0% 2.9%

165 159 3.1% 3.1% 0.0% 0.0% 0.0%

166 288 4.2% 2.1% 0.7% 0.0% 1.4%

167 106 24.5% 12.3% 8.5% 0.0% 3.8%

168 471 4.0% 2.5% 0.8% 0.0% 0.6%

169 198 1.5% 0.5% 0.0% 0.0% 1.0%

170 118 7.6% 5.1% 1.7% 0.0% 0.8%

171 362 3.3% 3.3% 0.0% 0.0% 0.0%

172 431 3.0% 1.9% 0.7% 0.0% 0.5%

173 151 23.2% 4.6% 10.6% 1.3% 6.6%

174 372 3.2% 2.7% 0.0% 0.3% 0.3%

175 330 2.7% 2.1% 0.0% 0.0% 0.6%

176 74 8.1% 5.4% 2.7% 0.0% 0.0%

177 470 3.8% 3.2% 0.2% 0.0% 0.4%

178 220 3.6% 3.2% 0.5% 0.0% 0.0%

179 137 12.4% 7.3% 4.4% 0.7% 0.0%

180 339 5.6% 4.1% 1.5% 0.0% 0.0%

181 230 8.7% 5.2% 3.0% 0.0% 0.4%

(8)

182 162 6.8% 5.6% 0.0% 0.0% 1.2%

183 95 23.2% 13.7% 5.3% 2.1% 2.1%

184 202 3.0% 1.5% 0.0% 0.0% 1.5%

185 422 6.6% 3.8% 1.2% 0.7% 0.9%

186 94 4.3% 2.1% 0.0% 2.1% 0.0%

187 162 7.4% 5.6% 1.2% 0.6% 0.0%

188 275 1.8% 1.1% 0.0% 0.0% 0.7%

189 395 1.3% 1.0% 0.3% 0.0% 0.0%

190 353 0.8% 0.8% 0.0% 0.0% 0.0%

191 132 9.1% 5.3% 1.5% 0.0% 2.3%

192 305 1.6% 0.0% 1.6% 0.0% 0.0%

193 489 6.5% 2.7% 1.6% 1.4% 0.8%

194 317 3.5% 2.5% 0.9% 0.0% 0.0%

195 306 7.2% 5.9% 1.3% 0.0% 0.0%

196 323 2.2% 1.5% 0.6% 0.0% 0.0%

197 452 6.0% 5.1% 0.4% 0.2% 0.2%

198 458 4.4% 3.1% 0.4% 0.7% 0.2%

199 319 4.1% 1.9% 0.3% 0.0% 1.9%

200 100 6.0% 6.0% 0.0% 0.0% 0.0%

201 307 10.1% 7.5% 2.0% 0.7% 0.0%

202 104 9.6% 6.7% 2.9% 0.0% 0.0%

203 106 4.7% 3.8% 0.9% 0.0% 0.0%

204 182 15.4% 4.4% 9.9% 1.1% 0.0%

205 213 0.5% 0.5% 0.0% 0.0% 0.0%

206 130 6.9% 5.4% 0.8% 0.0% 0.8%

207 176 33.0% 0.0% 21.6% 5.7% 5.7%

208 100 5.0% 5.0% 0.0% 0.0% 0.0%

209 215 7.0% 5.1% 1.4% 0.5% 0.0%

210 238 5.5% 5.0% 0.4% 0.0% 0.0%

211 358 6.4% 4.7% 0.6% 0.0% 1.1%

212 192 7.3% 5.7% 0.5% 0.0% 1.0%

213 176 5.1% 3.4% 0.6% 0.0% 1.1%

214 118 20.3% 9.3% 10.2% 0.0% 0.8%

215 356 3.1% 1.1% 0.6% 0.0% 1.4%

216 211 16.6% 2.4% 0.0% 0.0% 14.2%

217 430 9.8% 2.6% 5.3% 0.0% 1.9%

218 99 12.1% 7.1% 3.0% 0.0% 2.0%

219 273 11.7% 5.5% 1.5% 0.0% 4.8%

220 179 5.0% 2.2% 2.8% 0.0% 0.0%

221 219 3.2% 3.2% 0.0% 0.0% 0.0%

222 221 8.1% 5.4% 1.8% 0.0% 0.9%

223 134 5.2% 5.2% 0.0% 0.0% 0.0%

224 203 1.5% 0.0% 0.0% 0.0% 1.5%

225 247 3.6% 2.0% 0.4% 0.0% 1.2%

226 121 8.3% 5.0% 0.8% 1.7% 0.8%

227 109 18.3% 11.9% 1.8% 0.0% 4.6%

228 258 5.8% 3.9% 1.6% 0.4% 0.0%

229 209 11.0% 6.7% 2.4% 0.5% 1.4%

230 62 1.6% 0.0% 0.0% 0.0% 1.6%

231 163 6.7% 2.5% 2.5% 1.8% 0.0%

232 150 10.7% 8.0% 2.7% 0.0% 0.0%

min 0.0% 0.0% 0.0% 0.0% 0.0%

max 100.0% 23.0% 86.2% 87.2% 100.0%

ALK_S: ALK positive cells with short split ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D)

(9)

Supplemental data

ALK_S: ALK positive cells with short split ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern

Figure S3: ALK FISH patterns distribution in the entire cohort of lung ADC patients (n=232) .

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

ALK_S ALK_L ALK_FA ALK_D

(10)

Supplemental data

Table S4: Raw data of ALK FISH patterns and ALK gene status in ALK+ lung ADC patients (n=28)

# case # cells

scored ALK_R ALK_S ALK_L ALK_FA ALK_D prevalent split

pattern ALK copy number

145 305 15.0% 0.0% 9.0% 0.0% 6.0% long normal

204 182 15.4% 4.4% 9.9% 1.1% 0.0% long polysomy

143 202 15.8% 0.0% 13.9% 0.0% 2.0% long polysomy

216 211 16.6% 2.4% 0.0% 0.0% 14.2% deleted polysomy and amplification

227 109 18.3% 11.9% 1.8% 0.0% 4.6% short normal

214 118 20.3% 9.3% 10.2% 0.0% 0.8% long polysomy

40 300 20.7% 18.0% 2.7% 0.0% 0.0% short polysomy

62 148 20.9% 19.6% 0.7% 0.7% 0.0% short polysomy

61 100 23.0% 23.0% 0.0% 0.0% 0.0% short polysomy

183 95 23.2% 13.7% 5.3% 2.1% 2.1% short polysomy

173 151 23.2% 4.6% 10.6% 1.3% 6.6% long polysomy

167 106 24.5% 12.3% 8.5% 0.0% 3.8% short polysomy and amplification

104 312 25.6% 21.8% 2.2% 0.3% 1.3% short polysomy

32 375 26.7% 13.9% 8.3% 1.6% 2.9% short polysomy

10 100 29.0% 0.0% 3.0% 0.0% 26.0% deleted polysomy

142 350 31.4% 2.6% 4.0% 0.0% 24.9% deleted normal

207 176 33.0% 0.0% 21.6% 5.7% 5.7% long polysomy

56 85 44.7% 0.0% 1.2% 0.0% 43.5% deleted polysomy

5 58 65.5% 0.0% 0.0% 0.0% 65.5% deleted polysomy

69 127 68.5% 11.0% 6.3% 5.5% 45.7% deleted normal

106 100 85.0% 0.0% 4.0% 0.0% 81.0% deleted normal

138 86 88.4% 0.0% 0.0% 87.2% 1.2% far away normal

22 89 88.8% 0.0% 5.6% 0.0% 83.1% deleted normal

148 77 92.2% 7.8% 79.2% 3.9% 1.3% long normal

15 58 93.1% 5.2% 86.2% 1.7% 0.0% long normal

110 64 95.3% 15.6% 75.0% 0.0% 4.7% long normal

121 102 98.0% 0.0% 0.0% 0.0% 98.0% deleted polysomy

81 100 100.0% 0.0% 0.0% 0.0% 100.0% deleted normal

min 15.0% 0.0% 0.0% 0.0% 0.0%

max 100.0% 23.0% 86.2% 87.2% 100.0%

# prevalent short 8

# prevalent long 9

# prevalent deleted 10

# prevalent far away 1

# tot 28

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D) ALK_S: ALK positive cells with short split

ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern

(11)

Supplemental data

# case # cells

scored ALK_R ALK_S ALK_L ALK_FA ALK_D prevalent split

pattern ALK IHC

117 100 10.0% 7.0% 0.0% 0.0% 3.0% short negative

118 110 10.0% 0.9% 6.4% 0.0% 2.7% long negative

92 239 10.0% 7.9% 2.1% 0.0% 0.0% short n.a.*

201 307 10.1% 7.5% 2.0% 0.7% 0.0% short n.a.**

13 187 10.2% 3.7% 4.8% 0.5% 1.1% long n.a.*

72 369 10.3% 5.7% 4.1% 0.0% 0.5% short negative

59 132 10.6% 10.6% 0.0% 0.0% 0.0% short n.a.*

35 282 10.6% 8.2% 1.4% 0.7% 0.4% short negative

232 150 10.7% 8.0% 2.7% 0.0% 0.0% short negative

109 92 10.9% 10.9% 0.0% 0.0% 0.0% short negative

229 209 11.0% 6.7% 2.4% 0.5% 1.4% short negative

219 273 11.7% 5.5% 1.5% 0.0% 4.8% short negative

218 99 12.1% 7.1% 3.0% 0.0% 2.0% short negative

179 137 12.4% 7.3% 4.4% 0.7% 0.0% short n.a.**

97 279 12.5% 8.6% 3.9% 0.0% 0.0% short n.a.*

100 533 12.9% 12.9% 0.0% 0.0% 0.0% short n.a.**

93 413 13.6% 13.6% 0.0% 0.0% 0.0% short negative

min 10.0% 0.9% 0.0% 0.0% 0.0%

max 13.6% 13.6% 6.4% 0.7% 4.8%

# case # cells

scored ALK_R ALK_S ALK_L ALK_FA ALK_D prevalent split

pattern ALK IHC

145 305 15.0% 0.0% 9.0% 0.0% 6.0% long negative

204 182 15.4% 4.4% 9.9% 1.1% 0.0% long n.a.**

143 202 15.8% 0.0% 13.9% 0.0% 2.0% long n.a.*

216 211 16.6% 2.4% 0.0% 0.0% 14.2% deleted negative

227 109 18.3% 11.9% 1.8% 0.0% 4.6% short negative

214 118 20.3% 9.3% 10.2% 0.0% 0.8% long n.a.**

min 15.0% 0.0% 0.0% 0.0% 0.0%

max 20.3% 11.9% 13.9% 1.1% 14.2%

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D) ALK_S: ALK positive cells with short split

ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern n.a. : not available

* too small amount of neoplastic cells available

** cytological sample, FISH performed on Papanicolaou stained slide, no slides remained for IHC test

Table S5: Raw data of ALK FISH patterns and ALK protein status by IHC in ALK borderline lung ADCs.

Borderline ALK- (in first box) are those with ALK_R in a range of 10-15% (n=17).

Borderline ALK+ (second box) are those with ALK_R in a range of 15-20% (n=6).

(12)

Supplemental data

Table S6: Raw data of ALK FISH patterns in ALK- lung ADC patients (n=204)

# case # cells

scored ALK_R ALK_S ALK_L ALK_FA ALK_D prevalent split pattern

1 200 0.0% 0.0% 0.0% 0.0% 0.0% -

2 100 0.0% 0.0% 0.0% 0.0% 0.0% -

3 120 0.0% 0.0% 0.0% 0.0% 0.0% -

4 616 0.0% 0.0% 0.0% 0.0% 0.0% -

36 70 0.0% 0.0% 0.0% 0.0% 0.0% -

114 100 0.0% 0.0% 0.0% 0.0% 0.0% -

120 105 0.0% 0.0% 0.0% 0.0% 0.0% -

140 300 0.0% 0.0% 0.0% 0.0% 0.0% -

20 463 0.2% 0.2% 0.0% 0.0% 0.0% short

28 298 0.3% 0.0% 0.3% 0.0% 0.0% long

205 213 0.5% 0.5% 0.0% 0.0% 0.0% short

8 600 0.5% 0.0% 0.5% 0.0% 0.0% long

19 200 0.5% 0.5% 0.0% 0.0% 0.0% short

160 191 0.5% 0.5% 0.0% 0.0% 0.0% short

39 372 0.5% 0.5% 0.0% 0.0% 0.0% short

25 311 0.6% 0.0% 0.6% 0.0% 0.0% long

6 276 0.7% 0.0% 0.7% 0.0% 0.0% long

34 664 0.8% 0.0% 0.6% 0.0% 0.2% long

95 255 0.8% 0.4% 0.0% 0.0% 0.4% n.a.

190 353 0.8% 0.8% 0.0% 0.0% 0.0% short

49 220 0.9% 0.0% 0.0% 0.0% 0.9% deleted

122 105 1.0% 1.0% 0.0% 0.0% 0.0% short

139 310 1.0% 0.6% 0.3% 0.0% 0.0% short

12 309 1.0% 0.0% 0.6% 0.0% 0.3% long

130 203 1.0% 0.5% 0.0% 0.5% 0.0% n.a.

115 101 1.0% 1.0% 0.0% 0.0% 0.0% short

26 200 1.0% 1.0% 0.0% 0.0% 0.0% short

162 270 1.1% 1.1% 0.0% 0.0% 0.0% short

30 352 1.1% 0.0% 1.1% 0.0% 0.0% long

58 173 1.2% 0.6% 0.0% 0.0% 0.6% n.a.

9 336 1.2% 0.0% 1.2% 0.0% 0.0% long

65 252 1.2% 1.2% 0.0% 0.0% 0.0% short

29 500 1.2% 0.0% 1.0% 0.0% 0.2% long

189 395 1.3% 1.0% 0.3% 0.0% 0.0% short

157 308 1.3% 1.3% 0.0% 0.0% 0.0% short

31 447 1.3% 0.4% 0.9% 0.0% 0.0% long

52 147 1.4% 0.7% 0.0% 0.0% 0.7% n.a.

46 406 1.5% 0.7% 0.5% 0.0% 0.2% short

224 203 1.5% 0.0% 0.0% 0.0% 1.5% deleted

169 198 1.5% 0.5% 0.0% 0.0% 1.0% deleted

21 436 1.6% 0.9% 0.7% 0.0% 0.0% short

230 62 1.6% 0.0% 0.0% 0.0% 1.6% deleted

86 183 1.6% 1.1% 0.0% 0.0% 0.5% short

192 305 1.6% 0.0% 1.6% 0.0% 0.0% long

94 299 1.7% 1.7% 0.0% 0.0% 0.0% short

85 400 1.8% 1.3% 0.5% 0.0% 0.0% short

111 113 1.8% 0.0% 0.0% 0.0% 1.8% deleted

188 275 1.8% 1.1% 0.0% 0.0% 0.7% short

153 209 1.9% 1.4% 0.5% 0.0% 0.0% short

103 310 1.9% 0.3% 0.0% 0.0% 1.6% deleted

151 1323 2.0% 1.3% 0.2% 0.0% 0.5% short

126 101 2.0% 2.0% 0.0% 0.0% 0.0% short

137 618 2.1% 1.5% 0.3% 0.0% 0.3% short

196 323 2.2% 1.5% 0.6% 0.0% 0.0% short

54 137 2.2% 0.0% 0.7% 0.0% 1.5% deleted

16 500 2.2% 0.6% 0.4% 0.0% 1.2% deleted

(13)

75 402 2.2% 1.5% 0.5% 0.0% 0.2% short

45 130 2.3% 1.5% 0.8% 0.0% 0.0% short

38 950 2.3% 1.3% 0.7% 0.1% 0.2% short

51 205 2.4% 2.0% 0.0% 0.0% 0.5% short

42 400 2.5% 2.0% 0.3% 0.0% 0.3% short

132 257 2.7% 2.7% 0.0% 0.0% 0.0% short

175 330 2.7% 2.1% 0.0% 0.0% 0.6% short

55 309 2.9% 2.3% 0.6% 0.0% 0.0% short

60 240 2.9% 2.5% 0.4% 0.0% 0.0% short

159 375 2.9% 2.4% 0.0% 0.0% 0.5% short

129 101 3.0% 3.0% 0.0% 0.0% 0.0% short

184 202 3.0% 1.5% 0.0% 0.0% 1.5% n.a.

119 100 3.0% 3.0% 0.0% 0.0% 0.0% short

172 431 3.0% 1.9% 0.7% 0.0% 0.5% short

215 356 3.1% 1.1% 0.6% 0.0% 1.4% deleted

64 710 3.1% 2.3% 0.7% 0.1% 0.0% short

11 160 3.1% 0.0% 2.5% 0.6% 0.0% long

165 159 3.1% 3.1% 0.0% 0.0% 0.0% short

156 313 3.2% 2.6% 0.0% 0.0% 0.6% short

221 219 3.2% 3.2% 0.0% 0.0% 0.0% short

133 311 3.2% 2.9% 0.0% 0.0% 0.3% short

174 372 3.2% 2.7% 0.0% 0.3% 0.3% short

67 400 3.3% 3.3% 0.0% 0.0% 0.0% short

150 1304 3.3% 2.3% 0.2% 0.0% 0.8% short

171 362 3.3% 3.3% 0.0% 0.0% 0.0% short

24 180 3.3% 2.8% 0.0% 0.0% 0.6% short

78 412 3.4% 2.7% 0.2% 0.0% 0.5% short

194 317 3.5% 2.5% 0.9% 0.0% 0.0% short

17 200 3.5% 3.5% 0.0% 0.0% 0.0% short

144 228 3.5% 0.0% 3.5% 0.0% 0.0% long

178 220 3.6% 3.2% 0.5% 0.0% 0.0% short

225 247 3.6% 2.0% 0.4% 0.0% 1.2% short

146 1186 3.7% 0.0% 3.1% 0.0% 0.6% long

50 376 3.7% 2.9% 0.5% 0.0% 0.3% short

53 184 3.8% 2.7% 0.0% 0.0% 1.1% short

27 472 3.8% 0.0% 2.8% 0.2% 0.8% long

48 209 3.8% 3.3% 0.0% 0.0% 0.5% short

177 470 3.8% 3.2% 0.2% 0.0% 0.4% short

128 103 3.9% 3.9% 0.0% 0.0% 0.0% short

91 487 3.9% 3.3% 0.2% 0.0% 0.4% short

18 300 4.0% 2.0% 0.3% 0.0% 1.7% short

131 422 4.0% 3.3% 0.2% 0.0% 0.5% short

168 471 4.0% 2.5% 0.8% 0.0% 0.6% short

134 321 4.0% 3.7% 0.3% 0.0% 0.0% short

199 319 4.1% 1.9% 0.3% 0.0% 1.9% n.a.

79 313 4.2% 1.9% 1.0% 0.3% 1.0% short

166 288 4.2% 2.1% 0.7% 0.0% 1.4% short

77 571 4.2% 3.2% 0.7% 0.0% 0.4% short

186 94 4.3% 2.1% 0.0% 2.1% 0.0% n.a.

87 209 4.3% 3.3% 0.5% 0.0% 0.5% short

74 621 4.3% 3.1% 1.1% 0.0% 0.2% short

198 458 4.4% 3.1% 0.4% 0.7% 0.2% short

99 113 4.4% 4.4% 0.0% 0.0% 0.0% short

37 422 4.5% 2.8% 0.7% 0.5% 0.5% short

44 420 4.5% 3.1% 0.7% 0.0% 0.7% short

33 329 4.6% 0.3% 3.0% 0.0% 1.2% long

47 128 4.7% 3.1% 0.0% 0.0% 1.6% short

203 106 4.7% 3.8% 0.9% 0.0% 0.0% short

84 210 4.8% 3.8% 0.5% 0.0% 0.5% short

14 208 4.8% 2.4% 1.0% 0.0% 1.4% short

147 389 4.9% 0.0% 3.6% 0.0% 1.3% long

89 368 4.9% 4.3% 0.5% 0.0% 0.0% short

(14)

57 102 4.9% 2.0% 0.0% 2.0% 1.0% n.a.

7 122 4.9% 0.0% 3.3% 0.0% 1.6% long

158 222 5.0% 4.5% 0.0% 0.0% 0.5% short

98 100 5.0% 5.0% 0.0% 0.0% 0.0% short

208 100 5.0% 5.0% 0.0% 0.0% 0.0% short

220 179 5.0% 2.2% 2.8% 0.0% 0.0% long

141 433 5.1% 2.5% 1.4% 0.2% 0.9% short

213 176 5.1% 3.4% 0.6% 0.0% 1.1% short

223 134 5.2% 5.2% 0.0% 0.0% 0.0% short

90 210 5.2% 4.8% 0.5% 0.0% 0.0% short

41 434 5.3% 3.7% 0.7% 0.0% 0.9% short

210 238 5.5% 5.0% 0.4% 0.0% 0.0% short

88 365 5.5% 4.4% 0.5% 0.0% 0.5% short

116 109 5.5% 5.5% 0.0% 0.0% 0.0% short

161 72 5.6% 4.2% 0.0% 0.0% 1.4% short

180 339 5.6% 4.1% 1.5% 0.0% 0.0% short

70 372 5.6% 2.2% 0.5% 0.3% 2.7% deleted

152 956 5.6% 3.6% 0.1% 0.0% 2.0% short

71 509 5.7% 5.7% 0.0% 0.0% 0.0% short

228 258 5.8% 3.9% 1.6% 0.4% 0.0% short

135 342 5.8% 4.7% 0.6% 0.3% 0.3% short

101 222 5.9% 1.4% 0.9% 0.0% 3.6% deleted

197 452 6.0% 5.1% 0.4% 0.2% 0.2% short

200 100 6.0% 6.0% 0.0% 0.0% 0.0% short

136 320 6.3% 5.9% 0.3% 0.0% 0.0% short

83 447 6.3% 4.0% 1.3% 0.0% 0.9% short

63 78 6.4% 2.6% 0.0% 0.0% 3.8% deleted

112 109 6.4% 4.6% 0.0% 0.0% 1.8% short

211 358 6.4% 4.7% 0.6% 0.0% 1.1% short

96 184 6.5% 5.4% 0.0% 0.0% 1.1% short

193 489 6.5% 2.7% 1.6% 1.4% 0.8% short

185 422 6.6% 3.8% 1.2% 0.7% 0.9% short

113 149 6.7% 4.7% 1.3% 0.0% 0.7% short

231 163 6.7% 2.5% 2.5% 1.8% 0.0% n.a.

182 162 6.8% 5.6% 0.0% 0.0% 1.2% short

149 528 6.8% 4.9% 1.3% 0.0% 0.6% short

206 130 6.9% 5.4% 0.8% 0.0% 0.8% short

209 215 7.0% 5.1% 1.4% 0.5% 0.0% short

125 100 7.0% 6.0% 1.0% 0.0% 0.0% short

155 112 7.1% 6.3% 0.0% 0.0% 0.9% short

105 529 7.2% 5.7% 0.9% 0.2% 0.4% short

195 306 7.2% 5.9% 1.3% 0.0% 0.0% short

212 192 7.3% 5.7% 0.5% 0.0% 1.0% short

187 162 7.4% 5.6% 1.2% 0.6% 0.0% short

170 118 7.6% 5.1% 1.7% 0.0% 0.8% short

43 896 7.8% 4.6% 2.2% 0.0% 1.0% short

127 102 7.8% 3.9% 2.0% 0.0% 2.0% short

176 74 8.1% 5.4% 2.7% 0.0% 0.0% short

222 221 8.1% 5.4% 1.8% 0.0% 0.9% short

107 293 8.2% 7.8% 0.3% 0.0% 0.0% short

226 121 8.3% 5.0% 0.8% 1.7% 0.8% short

102 343 8.5% 6.4% 0.6% 0.0% 1.5% short

82 364 8.5% 5.8% 1.4% 0.0% 1.4% short

163 258 8.5% 6.6% 0.8% 0.0% 1.2% short

181 230 8.7% 5.2% 3.0% 0.0% 0.4% short

164 103 8.7% 4.9% 1.0% 0.0% 2.9% short

73 544 8.8% 4.4% 2.6% 0.9% 0.9% short

124 102 8.8% 6.9% 2.0% 0.0% 0.0% short

76 333 9.0% 4.8% 3.9% 0.3% 0.0% short

191 132 9.1% 5.3% 1.5% 0.0% 2.3% short

66 395 9.1% 8.1% 1.0% 0.0% 0.0% short

23 420 9.3% 1.9% 5.0% 1.0% 1.4% long

(15)

123 86 9.3% 9.3% 0.0% 0.0% 0.0% short

154 236 9.3% 5.1% 0.8% 0.0% 3.4% short

108 405 9.4% 6.9% 1.2% 0.0% 1.2% short

68 400 9.5% 8.5% 1.0% 0.0% 0.0% short

202 104 9.6% 6.7% 2.9% 0.0% 0.0% short

80 621 9.7% 6.1% 1.4% 0.0% 2.1% short

217 430 9.8% 2.6% 5.3% 0.0% 1.9% long

117 100 10.0% 7.0% 0.0% 0.0% 3.0% short

118 110 10.0% 0.9% 6.4% 0.0% 2.7% long

92 239 10.0% 7.9% 2.1% 0.0% 0.0% short

201 307 10.1% 7.5% 2.0% 0.7% 0.0% short

13 187 10.2% 3.7% 4.8% 0.5% 1.1% long

72 369 10.3% 5.7% 4.1% 0.0% 0.5% short

59 132 10.6% 10.6% 0.0% 0.0% 0.0% short

35 282 10.6% 8.2% 1.4% 0.7% 0.4% short

232 150 10.7% 8.0% 2.7% 0.0% 0.0% short

109 92 10.9% 10.9% 0.0% 0.0% 0.0% short

229 209 11.0% 6.7% 2.4% 0.5% 1.4% short

219 273 11.7% 5.5% 1.5% 0.0% 4.8% short

218 99 12.1% 7.1% 3.0% 0.0% 2.0% short

179 137 12.4% 7.3% 4.4% 0.7% 0.0% short

97 279 12.5% 8.6% 3.9% 0.0% 0.0% short

100 533 12.9% 12.9% 0.0% 0.0% 0.0% short

93 413 13.6% 13.6% 0.0% 0.0% 0.0% short

min 0.0% 0.0% 0.0% 0.0% 0.0%

max 13.6% 13.6% 6.4% 2.1% 4.8%

# without split 8

# n.a. 9

# prevalent short 152

# prevalent long 23

# prevalent deleted 12

# tot 204

# with prevalent pattern observed 187

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D) ALK_S: ALK positive cells with short split

ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern

n.a.: not applicable, no prevalent split pattern observed

(16)

Supplemental data

ALK+

(n=28)

ALK-

(n=204) p value

sex 0.068

M 11 119

F 17 85

age 0.026

<50 6 15

≥50 22 189

ALK copy number 0.053

polysomy 17 161

normal 11 43

Table S7: Fisher's Exact Test for correlation between clinical

pathological data and ALK FISH results in lung ADC patients

(n=232)

(17)

Supplemental data

Table S8: Raw data of ALK FISH patterns in ALK negative panel of controls (n=48)

# # cells

scored ALK_R ALK_S ALK_L ALK_FA ALK_D prevalent split

pattern

1 306 10.1% 9.2% 1.0% 0.0% 0.0% short

2 512 2.1% 1.6% 0.2% 0.2% 0.2% short

3 307 11.1% 8.8% 0.7% 0.0% 1.6% short

4 534 4.5% 2.6% 0.6% 0.2% 1.1% short

5 134 11.2% 7.5% 0.7% 0.7% 2.2% short

6 226 13.3% 9.3% 1.3% 0.0% 2.7% short

7 269 7.8% 5.2% 1.1% 0.0% 1.5% short

8 219 10.5% 5.9% 2.3% 0.5% 1.8% short

9 533 5.4% 4.3% 0.8% 0.2% 0.2% short

10 250 12.0% 9.2% 2.4% 0.0% 0.4% short

11 163 6.1% 4.9% 0.6% 0.0% 0.6% short

12 162 7.4% 6.8% 0.6% 0.0% 0.0% short

13 168 7.7% 7.1% 0.0% 0.0% 0.6% short

14 161 6.8% 5.6% 0.6% 0.0% 0.6% short

15 150 4.7% 3.3% 0.0% 0.0% 1.3% short

16 165 4.2% 4.2% 0.0% 0.0% 0.0% short

17 156 2.6% 2.6% 0.0% 0.0% 0.0% short

18 146 4.1% 4.1% 0.0% 0.0% 0.0% short

19 212 5.2% 1.4% 3.3% 0.5% 0.0% long

20 214 6.1% 3.3% 1.9% 0.5% 0.5% short

21 206 2.4% 2.4% 0.0% 0.0% 0.0% short

22 206 2.9% 1.5% 1.0% 0.5% 0.0% short

23 204 2.0% 1.0% 0.5% 0.5% 0.0% short

24 133 4.5% 3.8% 0.8% 0.0% 0.0% short

25 166 4.8% 4.2% 0.0% 0.0% 0.6% short

26 158 5.1% 4.4% 0.6% 0.0% 0.0% short

27 211 4.7% 3.3% 0.5% 0.0% 0.9% short

28 206 2.4% 1.5% 0.5% 0.0% 0.5% short

29 212 4.7% 2.4% 1.9% 0.0% 0.5% short

30 221 9.0% 5.4% 0.5% 0.0% 3.2% short

31 214 6.5% 3.3% 1.9% 0.9% 0.5% short

32 218 6.9% 4.6% 1.4% 0.5% 0.5% short

33 180 4.4% 2.2% 0.6% 0.6% 1.1% short

34 111 9.9% 5.4% 3.6% 0.0% 0.9% short

35 326 8.0% 4.3% 2.1% 0.0% 1.5% short

36 213 7.5% 4.7% 1.9% 0.5% 0.5% short

37 221 8.6% 5.4% 1.4% 0.9% 0.9% short

38 220 7.3% 3.6% 2.3% 0.5% 0.9% short

39 215 7.0% 5.1% 1.4% 0.0% 0.5% short

40 103 2.9% 2.9% 0.0% 0.0% 0.0% short

41 105 5.7% 2.9% 1.9% 0.0% 1.0% short

42 105 4.8% 2.9% 1.0% 0.0% 1.0% short

43 114 12.3% 4.4% 2.6% 0.9% 4.4% n.a.

44 215 5.1% 3.7% 0.9% 0.0% 0.5% short

45 212 5.2% 1.9% 0.9% 0.5% 1.9% n.a.

46 214 6.1% 3.7% 0.9% 0.5% 0.9% short

47 209 3.8% 3.3% 0.0% 0.0% 0.5% short

48 222 4.5% 1.8% 1.8% 0.0% 0.9% n.a.

min 2.0% 1.0% 0.0% 0.0% 0.0%

max 13.3% 9.3% 3.6% 0.9% 4.4%

Mean (M) 6.3%

standard deviation (SD) 2.9%

M+3DS 14.9%

# n.a. 3

# prevalent short 44

# prevalent long 1

# prevalent deleted 0

# tot 48

# with prevalent pattern observed 45

ALK_R: ALK rearranged cells (namey all cells with positive patterns, constituted by ALK_S+ALK_L+ALK_FA+ALK_D) ALK_S: ALK positive cells with short split

ALK_L: ALK positive cells with long split ALK_FA: ALK positive cells with far away split ALK_D: ALK positive cells with deleted pattern n.a.: not applicable, no prevalent split pattern observed

(18)

Supplemental data

ADCs all ALK+

(ALK_R≥15%)

borderline ALK+

(ALK_R=15-20%)

frank ALK+

(ALK_R>20%)

# 28 6 22

split pattern

short 8 1 7

non-short 20 5 15

ADCs all ALK-

(ALK_R<15%)

borderline ALK- (ALK_R=10-15%)

frank ALK- (ALK_R<10%)

# 204 17 187

split pattern

short 152 15 137

non-short 35 2 33

not applicable* 17 0 17

ALK negative controls

# 48

split pattern

short 44

non-short 1

not applicable* 3

* no split or no prevalent split pattern was observed in these cases

Table S9: Short split pattern distribution among ADC patients and

ALK negative controls

(19)

Supplemental data

all ALK+

(ALK_R≥15%)

frank ALK+

(ALK_R>20%) p value

# 28 22 1.0

split pattern

short 8 7

non-short 20 15

all ALK+

(ALK_R≥15%)

borderline ALK+

(ALK_R=15-20%) p value

# 28 6 1.0

split pattern

short 8 1

non-short 20 5

frank ALK+

(ALK_R>20%)

borderline ALK+

(ALK_R=15-20%) p value

# 22 6 0.639

split pattern

short 7 1

non-short 15 5

all ALK- (ALK_R<15%)

frank ALK-

(ALK_R<10%) p value

# 187^ 170^ 0.89 0.89

split pattern

short 152 137

non-short 35 33

all ALK- (ALK_R<15%)

borderline ALK-

(ALK_R=10-15%) p value

# 187^ 17 0.74

split pattern

short 152 15

non-short 35 2

frank ALK- (ALK_R<10%)

borderline ALK-

(ALK_R=10-15%) p value

# 170^ 17 0.74

split pattern

short 137 15

non-short 33 2

all ALK+

(ALK_R≥15%)

all ALK-

(ALK_R<15%) p value

# 28 187^ 0.00000005

split pattern

short 8 152

non-short 20 35

frank ALK+

(ALK_R>20%)

frank ALK-

(ALK_R<10%) p value

# 22 170^ 0.00000615

split pattern

short 7 137

non-short 15 33

Table S10: Raw data of correlation between the prevalent split pattern (short split

vs. non-short split) and ALK status in ADCs and negative controls by two-tailed

Fisher's Exact test

(20)

borderline ALK+

(ALK_R=15-20%)

borderline ALK-

(ALK_R=10-15%) p value

# 6 17 0.00339

split pattern

short 1 15

non-short 5 2

all ALK+

(ALK_R≥15%)

frank ALK-

(ALK_R<10%) p value

# 28 170^ 0.0000001

split pattern

short 8 137

non-short 20 33

all ALK+

(ALK_R≥15%)

borderline ALK-

(ALK_R=10-15%) p value

# 28 17 0.00014

split pattern

short 8 15

non-short 20 2

frank ALK+

(ALK_R>20%)

borderline ALK-

(ALK_R=10-15%) p value

# 22 17 0.00084

split pattern

short 7 15

non-short 15 2

all ALK- (ALK_R<15%)

frank ALK+

(ALK_R>20%) p value

# 187^ 22 0.00000356

split pattern

short 152 7

non-short 35 15

all ALK- (ALK_R<15%)

borderline ALK+

(ALK_R=15-20%) p value

# 187^ 6 0.00157

split pattern

short 152 1

non-short 35 5

borderline ALK+

(ALK_R=15-20%)

frank ALK-

(ALK_R<10%) p value

# 6 170^ 0.0019

split pattern

short 1 137

non-short 5 33

ALK negative controls

all ALK+

(ALK_R≥15%) p value

# 45^ 28 0.0015

split pattern

short 44 8

non-short 1 20

(21)

ALK negative controls

frank ALK+

(ALK_R>20%) p value

# 45^ 22 0.00000001

split pattern

short 44 7

non-short 1 15

ALK negative controls

borderline ALK+

(ALK_R=15-20%) p value

# 45^ 6 0.000015

split pattern

short 44 1

non-short 1 5

ALK negative controls

all ALK-

(ALK_R<15%) p value

# 45^ 187^ 0.0047

split pattern

short 44 152

non-short 1 35

ALK negative controls

frank ALK-

(ALK_R<10%) p value

# 45^ 187 0.0026

split pattern

short 44 137

non-short 1 33

ALK negative controls

borderline ALK-

(ALK_R=10-15%) p value

# 45^ 17 0.17

split pattern

short 44 15

non-short 1 2

^ cases for which a prevalent split pattern was assessable

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After the model is predicted, the results obtained from testing the Long short term memory model on 600 neurons and the distribution of test data of 20%.. With positive original data