Correlation between copy number variation genes (focal events) and selected clinical features
Skin Cutaneous Melanoma (Metastatic)
15 January 2014  |  analyses__2014_01_15
Maintainer Information
Citation Information
doi:10.7908/C1D21W3Z
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between copy number variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1D21W3Z
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and selected clinical features.

Summary

Testing the association between copy number variation 52 focal events and 12 clinical features across 260 patients, 2 significant findings detected with Q value < 0.25.

  • del_3p24.3 cnv correlated to 'BRESLOW.THICKNESS'.

  • del_10q26.3 cnv correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 52 focal events and 12 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.

Clinical
Features 		Time
from
Specimen
Diagnosis
to
Death 		Time
to
Death 		AGE PRIMARY
SITE
OF
DISEASE 		NEOPLASM
DISEASESTAGE 		PATHOLOGY
T
STAGE 		PATHOLOGY
N
STAGE 		PATHOLOGY
M
STAGE 		MELANOMA
ULCERATION 		MELANOMA
PRIMARY
KNOWN 		BRESLOW
THICKNESS 		GENDER
nCNV (%) nWild-Type logrank test logrank test t-test Fisher's exact test Chi-square test Fisher's exact test Fisher's exact test Chi-square test Fisher's exact test Fisher's exact test t-test Fisher's exact test
del 3p24 3 46 (18%) 214 0.299
(1.00) 		0.324
(1.00) 		0.246
(1.00) 		0.82
(1.00) 		0.406
(1.00) 		0.032
(1.00) 		0.0918
(1.00) 		0.779
(1.00) 		0.652
(1.00) 		0.454
(1.00) 		0.000302
(0.188) 		0.32
(1.00)
del 10q26 3 163 (63%) 97 0.514
(1.00) 		0.41
(1.00) 		0.000116
(0.0722) 		0.124
(1.00) 		0.841
(1.00) 		0.179
(1.00) 		0.759
(1.00) 		0.15
(1.00) 		0.871
(1.00) 		1
(1.00) 		0.631
(1.00) 		0.0489
(1.00)
amp 1p12 81 (31%) 179 0.07
(1.00) 		0.0256
(1.00) 		0.935
(1.00) 		0.633
(1.00) 		0.348
(1.00) 		0.508
(1.00) 		0.944
(1.00) 		0.508
(1.00) 		0.493
(1.00) 		1
(1.00) 		0.596
(1.00) 		1
(1.00)
amp 1q21 3 134 (52%) 126 0.533
(1.00) 		0.91
(1.00) 		0.837
(1.00) 		0.121
(1.00) 		0.524
(1.00) 		0.935
(1.00) 		0.32
(1.00) 		0.499
(1.00) 		0.421
(1.00) 		0.707
(1.00) 		0.957
(1.00) 		1
(1.00)
amp 1q44 140 (54%) 120 0.43
(1.00) 		0.0891
(1.00) 		0.882
(1.00) 		0.158
(1.00) 		0.543
(1.00) 		0.977
(1.00) 		0.702
(1.00) 		0.552
(1.00) 		0.423
(1.00) 		0.703
(1.00) 		0.42
(1.00) 		0.703
(1.00)
amp 3p13 69 (27%) 191 0.043
(1.00) 		0.00354
(1.00) 		0.0533
(1.00) 		0.95
(1.00) 		0.128
(1.00) 		0.0752
(1.00) 		0.441
(1.00) 		0.584
(1.00) 		0.585
(1.00) 		0.67
(1.00) 		0.0651
(1.00) 		0.151
(1.00)
amp 4q12 47 (18%) 213 0.464
(1.00) 		0.768
(1.00) 		0.297
(1.00) 		0.927
(1.00) 		0.327
(1.00) 		0.341
(1.00) 		0.735
(1.00) 		0.311
(1.00) 		0.676
(1.00) 		0.463
(1.00) 		0.597
(1.00) 		0.869
(1.00)
amp 5p15 33 83 (32%) 177 0.465
(1.00) 		0.196
(1.00) 		0.234
(1.00) 		0.363
(1.00) 		0.623
(1.00) 		0.189
(1.00) 		0.153
(1.00) 		0.354
(1.00) 		1
(1.00) 		0.221
(1.00) 		0.126
(1.00) 		1
(1.00)
amp 5q35 3 41 (16%) 219 0.251
(1.00) 		0.511
(1.00) 		0.881
(1.00) 		0.0307
(1.00) 		0.815
(1.00) 		0.338
(1.00) 		0.883
(1.00) 		0.415
(1.00) 		0.174
(1.00) 		1
(1.00) 		0.0977
(1.00) 		0.729
(1.00)
amp 6p24 3 144 (55%) 116 0.00125
(0.78) 		0.0464
(1.00) 		0.0225
(1.00) 		0.106
(1.00) 		0.233
(1.00) 		0.198
(1.00) 		0.819
(1.00) 		0.311
(1.00) 		0.626
(1.00) 		1
(1.00) 		0.664
(1.00) 		0.799
(1.00)
amp 6q12 56 (22%) 204 0.854
(1.00) 		0.928
(1.00) 		0.0767
(1.00) 		0.151
(1.00) 		0.218
(1.00) 		0.433
(1.00) 		0.677
(1.00) 		0.464
(1.00) 		0.249
(1.00) 		0.495
(1.00) 		0.383
(1.00) 		0.28
(1.00)
amp 7p22 1 141 (54%) 119 0.659
(1.00) 		0.598
(1.00) 		0.327
(1.00) 		0.677
(1.00) 		0.13
(1.00) 		0.186
(1.00) 		0.801
(1.00) 		0.416
(1.00) 		0.632
(1.00) 		0.126
(1.00) 		0.184
(1.00) 		1
(1.00)
amp 7q34 156 (60%) 104 0.899
(1.00) 		0.833
(1.00) 		0.163
(1.00) 		0.165
(1.00) 		0.0108
(1.00) 		0.509
(1.00) 		0.346
(1.00) 		0.657
(1.00) 		0.326
(1.00) 		0.436
(1.00) 		0.387
(1.00) 		0.0689
(1.00)
amp 8q11 21 112 (43%) 148 0.421
(1.00) 		0.317
(1.00) 		0.0295
(1.00) 		0.0268
(1.00) 		0.333
(1.00) 		0.222
(1.00) 		0.204
(1.00) 		0.376
(1.00) 		0.87
(1.00) 		0.0835
(1.00) 		0.937
(1.00) 		0.607
(1.00)
amp 8q24 21 131 (50%) 129 0.976
(1.00) 		0.403
(1.00) 		0.0234
(1.00) 		0.068
(1.00) 		0.387
(1.00) 		0.159
(1.00) 		0.228
(1.00) 		0.682
(1.00) 		1
(1.00) 		0.251
(1.00) 		0.933
(1.00) 		0.525
(1.00)
amp 9p24 1 24 (9%) 236 0.842
(1.00) 		0.469
(1.00) 		0.572
(1.00) 		0.00757
(1.00) 		0.236
(1.00) 		0.375
(1.00) 		0.767
(1.00) 		0.686
(1.00) 		0.0489
(1.00) 		1
(1.00) 		0.00131
(0.811) 		1
(1.00)
amp 11q13 3 49 (19%) 211 0.401
(1.00) 		0.797
(1.00) 		0.596
(1.00) 		0.129
(1.00) 		0.047
(1.00) 		0.026
(1.00) 		0.223
(1.00) 		0.56
(1.00) 		0.824
(1.00) 		0.624
(1.00) 		0.261
(1.00) 		0.871
(1.00)
amp 11q13 4 45 (17%) 215 0.439
(1.00) 		0.92
(1.00) 		0.226
(1.00) 		0.124
(1.00) 		0.356
(1.00) 		0.0526
(1.00) 		0.0797
(1.00) 		0.426
(1.00) 		0.505
(1.00) 		0.8
(1.00) 		0.15
(1.00) 		0.737
(1.00)
amp 12q14 1 46 (18%) 214 0.637
(1.00) 		0.139
(1.00) 		0.22
(1.00) 		0.586
(1.00) 		0.503
(1.00) 		0.272
(1.00) 		0.353
(1.00) 		0.604
(1.00) 		0.559
(1.00) 		0.128
(1.00) 		0.146
(1.00) 		1
(1.00)
amp 12q15 45 (17%) 215 0.544
(1.00) 		0.924
(1.00) 		0.206
(1.00) 		0.429
(1.00) 		0.763
(1.00) 		0.556
(1.00) 		0.353
(1.00) 		0.771
(1.00) 		0.686
(1.00) 		0.127
(1.00) 		0.522
(1.00) 		1
(1.00)
amp 15q26 2 87 (33%) 173 0.512
(1.00) 		0.183
(1.00) 		0.76
(1.00) 		0.501
(1.00) 		0.00273
(1.00) 		0.257
(1.00) 		0.565
(1.00) 		0.409
(1.00) 		0.289
(1.00) 		0.0696
(1.00) 		0.504
(1.00) 		1
(1.00)
amp 17q25 3 90 (35%) 170 0.379
(1.00) 		0.91
(1.00) 		0.00578
(1.00) 		0.537
(1.00) 		0.402
(1.00) 		0.143
(1.00) 		0.929
(1.00) 		0.962
(1.00) 		0.237
(1.00) 		0.843
(1.00) 		0.424
(1.00) 		0.229
(1.00)
amp 19p13 2 49 (19%) 211 0.86
(1.00) 		0.713
(1.00) 		0.704
(1.00) 		0.429
(1.00) 		0.234
(1.00) 		0.692
(1.00) 		0.735
(1.00) 		0.00126
(0.782) 		0.686
(1.00) 		0.624
(1.00) 		0.792
(1.00) 		0.871
(1.00)
amp 20q13 33 135 (52%) 125 0.993
(1.00) 		0.454
(1.00) 		0.0375
(1.00) 		0.456
(1.00) 		0.0849
(1.00) 		0.125
(1.00) 		0.257
(1.00) 		0.116
(1.00) 		0.2
(1.00) 		0.849
(1.00) 		0.109
(1.00) 		0.611
(1.00)
amp 22q13 2 111 (43%) 149 0.244
(1.00) 		0.371
(1.00) 		0.815
(1.00) 		0.546
(1.00) 		0.962
(1.00) 		0.142
(1.00) 		0.528
(1.00) 		0.961
(1.00) 		0.262
(1.00) 		1
(1.00) 		0.62
(1.00) 		0.898
(1.00)
del 1p36 31 61 (23%) 199 0.48
(1.00) 		0.772
(1.00) 		0.425
(1.00) 		0.3
(1.00) 		0.187
(1.00) 		0.731
(1.00) 		0.99
(1.00) 		0.121
(1.00) 		1
(1.00) 		1
(1.00) 		0.331
(1.00) 		0.23
(1.00)
del 1p22 1 67 (26%) 193 0.643
(1.00) 		0.5
(1.00) 		0.0658
(1.00) 		0.728
(1.00) 		0.0119
(1.00) 		0.951
(1.00) 		0.043
(1.00) 		0.0909
(1.00) 		0.0963
(1.00) 		0.665
(1.00) 		0.765
(1.00) 		0.249
(1.00)
del 2q37 3 64 (25%) 196 0.227
(1.00) 		0.972
(1.00) 		0.482
(1.00) 		0.306
(1.00) 		0.933
(1.00) 		0.458
(1.00) 		0.394
(1.00) 		0.125
(1.00) 		0.366
(1.00) 		0.657
(1.00) 		0.98
(1.00) 		0.769
(1.00)
del 3q23 39 (15%) 221 0.39
(1.00) 		0.645
(1.00) 		0.597
(1.00) 		0.786
(1.00) 		0.124
(1.00) 		0.238
(1.00) 		0.149
(1.00) 		0.115
(1.00) 		0.507
(1.00) 		0.591
(1.00) 		0.107
(1.00) 		1
(1.00)
del 4q34 3 68 (26%) 192 0.788
(1.00) 		0.733
(1.00) 		0.248
(1.00) 		0.419
(1.00) 		0.44
(1.00) 		0.168
(1.00) 		0.729
(1.00) 		0.171
(1.00) 		0.471
(1.00) 		0.393
(1.00) 		0.0829
(1.00) 		0.0308
(1.00)
del 5p15 31 55 (21%) 205 0.348
(1.00) 		0.487
(1.00) 		0.296
(1.00) 		0.901
(1.00) 		0.648
(1.00) 		0.0595
(1.00) 		0.727
(1.00) 		0.897
(1.00) 		0.0118
(1.00) 		0.348
(1.00) 		0.9
(1.00) 		0.163
(1.00)
del 5q11 2 72 (28%) 188 0.496
(1.00) 		0.642
(1.00) 		0.206
(1.00) 		0.841
(1.00) 		0.507
(1.00) 		0.0986
(1.00) 		0.525
(1.00) 		0.119
(1.00) 		0.151
(1.00) 		0.669
(1.00) 		0.469
(1.00) 		1
(1.00)
del 5q31 3 99 (38%) 161 0.962
(1.00) 		0.924
(1.00) 		0.703
(1.00) 		0.912
(1.00) 		0.858
(1.00) 		0.0639
(1.00) 		0.414
(1.00) 		0.151
(1.00) 		0.743
(1.00) 		0.168
(1.00) 		0.959
(1.00) 		1
(1.00)
del 6q26 160 (62%) 100 0.335
(1.00) 		0.759
(1.00) 		0.612
(1.00) 		0.683
(1.00) 		0.655
(1.00) 		0.523
(1.00) 		0.845
(1.00) 		0.97
(1.00) 		0.188
(1.00) 		0.326
(1.00) 		0.115
(1.00) 		0.0891
(1.00)
del 8p23 3 61 (23%) 199 0.273
(1.00) 		0.684
(1.00) 		0.187
(1.00) 		0.102
(1.00) 		0.434
(1.00) 		0.0779
(1.00) 		0.388
(1.00) 		0.664
(1.00) 		0.453
(1.00) 		0.498
(1.00) 		0.139
(1.00) 		0.881
(1.00)
del 9p23 176 (68%) 84 0.0934
(1.00) 		0.648
(1.00) 		0.662
(1.00) 		0.524
(1.00) 		0.795
(1.00) 		0.708
(1.00) 		0.653
(1.00) 		0.175
(1.00) 		0.611
(1.00) 		0.686
(1.00) 		0.735
(1.00) 		0.136
(1.00)
del 9p21 3 197 (76%) 63 0.135
(1.00) 		0.753
(1.00) 		0.427
(1.00) 		0.202
(1.00) 		0.735
(1.00) 		0.671
(1.00) 		0.875
(1.00) 		0.561
(1.00) 		1
(1.00) 		0.178
(1.00) 		0.414
(1.00) 		0.0742
(1.00)
del 10p15 3 139 (53%) 121 0.118
(1.00) 		0.618
(1.00) 		0.0163
(1.00) 		0.227
(1.00) 		0.943
(1.00) 		0.126
(1.00) 		0.921
(1.00) 		0.837
(1.00) 		0.631
(1.00) 		1
(1.00) 		0.793
(1.00) 		0.129
(1.00)
del 10q23 31 160 (62%) 100 0.522
(1.00) 		0.731
(1.00) 		0.00675
(1.00) 		0.129
(1.00) 		0.904
(1.00) 		0.0919
(1.00) 		0.409
(1.00) 		0.308
(1.00) 		0.512
(1.00) 		0.326
(1.00) 		0.975
(1.00) 		0.026
(1.00)
del 11p11 2 84 (32%) 176 0.541
(1.00) 		0.412
(1.00) 		0.0488
(1.00) 		0.449
(1.00) 		0.476
(1.00) 		0.402
(1.00) 		0.658
(1.00) 		0.527
(1.00) 		0.31
(1.00) 		0.54
(1.00) 		0.882
(1.00) 		0.00268
(1.00)
del 11q23 3 141 (54%) 119 0.592
(1.00) 		0.674
(1.00) 		0.268
(1.00) 		0.283
(1.00) 		0.544
(1.00) 		0.437
(1.00) 		0.751
(1.00) 		0.828
(1.00) 		0.746
(1.00) 		0.848
(1.00) 		0.338
(1.00) 		0.203
(1.00)
del 12q23 3 60 (23%) 200 0.8
(1.00) 		0.573
(1.00) 		0.677
(1.00) 		0.766
(1.00) 		0.936
(1.00) 		0.878
(1.00) 		0.785
(1.00) 		0.47
(1.00) 		1
(1.00) 		1
(1.00) 		0.266
(1.00) 		0.0975
(1.00)
del 13q12 11 62 (24%) 198 0.454
(1.00) 		0.472
(1.00) 		0.622
(1.00) 		0.608
(1.00) 		0.889
(1.00) 		0.0911
(1.00) 		0.694
(1.00) 		0.0201
(1.00) 		1
(1.00) 		0.656
(1.00) 		0.0426
(1.00) 		0.138
(1.00)
del 13q34 60 (23%) 200 0.531
(1.00) 		0.498
(1.00) 		0.837
(1.00) 		0.412
(1.00) 		0.503
(1.00) 		0.523
(1.00) 		0.494
(1.00) 		0.0166
(1.00) 		0.719
(1.00) 		1
(1.00) 		0.239
(1.00) 		0.763
(1.00)
del 14q32 2 87 (33%) 173 0.727
(1.00) 		0.962
(1.00) 		0.458
(1.00) 		0.519
(1.00) 		0.157
(1.00) 		0.351
(1.00) 		0.272
(1.00) 		0.304
(1.00) 		1
(1.00) 		0.84
(1.00) 		0.16
(1.00) 		0.591
(1.00)
del 15q13 3 60 (23%) 200 0.158
(1.00) 		0.0978
(1.00) 		0.338
(1.00) 		0.981
(1.00) 		0.64
(1.00) 		0.0814
(1.00) 		0.403
(1.00) 		0.833
(1.00) 		1
(1.00) 		0.82
(1.00) 		0.978
(1.00) 		1
(1.00)
del 15q14 61 (23%) 199 0.033
(1.00) 		0.0591
(1.00) 		0.749
(1.00) 		0.943
(1.00) 		0.132
(1.00) 		0.188
(1.00) 		0.25
(1.00) 		0.564
(1.00) 		0.571
(1.00) 		0.657
(1.00) 		0.864
(1.00) 		0.764
(1.00)
del 15q15 2 64 (25%) 196 0.119
(1.00) 		0.241
(1.00) 		0.62
(1.00) 		0.834
(1.00) 		0.228
(1.00) 		0.397
(1.00) 		0.251
(1.00) 		0.557
(1.00) 		0.453
(1.00) 		0.657
(1.00) 		0.814
(1.00) 		0.557
(1.00)
del 16p13 3 51 (20%) 209 0.669
(1.00) 		0.826
(1.00) 		0.0891
(1.00) 		0.474
(1.00) 		0.948
(1.00) 		0.442
(1.00) 		0.439
(1.00) 		0.512
(1.00) 		1
(1.00) 		0.0541
(1.00) 		0.268
(1.00) 		0.201
(1.00)
del 16q12 1 85 (33%) 175 0.424
(1.00) 		0.28
(1.00) 		0.305
(1.00) 		0.486
(1.00) 		0.445
(1.00) 		0.612
(1.00) 		0.387
(1.00) 		0.536
(1.00) 		1
(1.00) 		0.423
(1.00) 		0.985
(1.00) 		0.282
(1.00)
del 16q24 3 92 (35%) 168 0.245
(1.00) 		0.192
(1.00) 		0.137
(1.00) 		0.573
(1.00) 		0.0318
(1.00) 		0.745
(1.00) 		0.102
(1.00) 		0.624
(1.00) 		1
(1.00) 		0.317
(1.00) 		0.877
(1.00) 		0.288
(1.00)
del 19p13 3 75 (29%) 185 0.408
(1.00) 		0.365
(1.00) 		0.671
(1.00) 		0.349
(1.00) 		0.685
(1.00) 		0.375
(1.00) 		0.394
(1.00) 		0.299
(1.00) 		0.598
(1.00) 		0.834
(1.00) 		0.0705
(1.00) 		0.206
(1.00)
'del_3p24.3' versus 'BRESLOW.THICKNESS'

P value = 0.000302 (t-test), Q value = 0.19

Table S1.  Gene #27: 'del_3p24.3' versus Clinical Feature #11: 'BRESLOW.THICKNESS'

nPatients Mean (Std.Dev)
ALL 192 3.6 (5.1)
DEL PEAK 4(3P24.3) MUTATED 33 2.0 (1.6)
DEL PEAK 4(3P24.3) WILD-TYPE 159 3.9 (5.5)

Figure S1.  Get High-res Image Gene #27: 'del_3p24.3' versus Clinical Feature #11: 'BRESLOW.THICKNESS'

'del_10q26.3' versus 'AGE'

P value = 0.000116 (t-test), Q value = 0.072

Table S2.  Gene #39: 'del_10q26.3' versus Clinical Feature #3: 'AGE'

nPatients Mean (Std.Dev)
ALL 256 55.6 (15.8)
DEL PEAK 16(10Q26.3) MUTATED 159 52.7 (16.1)
DEL PEAK 16(10Q26.3) WILD-TYPE 97 60.3 (14.1)

Figure S2.  Get High-res Image Gene #39: 'del_10q26.3' versus Clinical Feature #3: 'AGE'

Methods & Data
Input

  • Copy number data file = transformed.cor.cli.txt

  • Clinical data file = SKCM-TM.merged_data.txt

  • Number of patients = 260

  • Number of significantly focal cnvs = 52

  • Number of selected clinical features = 12

  • Exclude genes that fewer than K tumors have mutations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene mutations were plotted and the statistical significance P values were estimated by logrank test (Bland and Altman 2004) using the 'survdiff' function in R

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' function in R

Fisher's exact test

For binary or multi-class clinical features (nominal or ordinal), two-tailed Fisher's exact tests (Fisher 1922) were used to estimate the P values using the 'fisher.test' function in R

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.test' function in R

Q value calculation

For multiple hypothesis correction, Q value is the False Discovery Rate (FDR) analogue of the P value (Benjamini and Hochberg 1995), defined as the minimum FDR at which the test may be called significant. We used the 'Benjamini and Hochberg' method of 'p.adjust' function in R to convert P values into Q values.

Download Results

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References
[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] Fisher, R.A., On the interpretation of chi-square from contingency tables, and the calculation of P, Journal of the Royal Statistical Society 85(1):87-94 (1922)
[4] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[5] Benjamini and Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, Journal of the Royal Statistical Society Series B 59:289-300 (1995)
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