Skin Cutaneous Melanoma: Correlation between copy number variations of arm-level result and selected clinical features
(All_Metastatic cohort)
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Overview
Introduction

This pipeline computes the correlation between significant arm-level copy number variations (cnvs) and selected clinical features.

Summary

Testing the association between copy number variation 77 arm-level results and 8 clinical features across 173 patients, 2 significant findings detected with Q value < 0.25.

  • 18p gain cnv correlated to 'NEOPLASM.DISEASESTAGE'.

  • 18q gain cnv correlated to 'NEOPLASM.DISEASESTAGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 77 arm-level results and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE PRIMARY
SITE
OF
DISEASE 		GENDER DISTANT
METASTASIS 		LYMPH
NODE
METASTASIS 		TUMOR
STAGECODE 		NEOPLASM
DISEASESTAGE
nCNV (%) nWild-Type logrank test t-test Fisher's exact test Fisher's exact test Chi-square test Chi-square test t-test Chi-square test
18p gain 22 (13%) 151 0.822
(1.00) 		0.0745
(1.00) 		0.744
(1.00) 		0.252
(1.00) 		0.516
(1.00) 		0.429
(1.00) 		2.58e-05
(0.0136)
18q gain 12 (7%) 161 0.95
(1.00) 		0.506
(1.00) 		0.213
(1.00) 		0.541
(1.00) 		0.96
(1.00) 		0.49
(1.00) 		1.16e-07
(6.15e-05)
1p gain 22 (13%) 151 0.134
(1.00) 		0.142
(1.00) 		0.414
(1.00) 		0.492
(1.00) 		0.863
(1.00) 		0.382
(1.00) 		0.0462
(1.00)
1q gain 59 (34%) 114 0.318
(1.00) 		0.778
(1.00) 		0.11
(1.00) 		1
(1.00) 		0.638
(1.00) 		0.217
(1.00) 		0.519
(1.00)
2p gain 18 (10%) 155 0.679
(1.00) 		0.17
(1.00) 		0.59
(1.00) 		0.444
(1.00) 		0.907
(1.00) 		0.159
(1.00) 		0.818
(1.00)
2q gain 16 (9%) 157 0.863
(1.00) 		0.432
(1.00) 		0.578
(1.00) 		0.599
(1.00) 		0.927
(1.00) 		0.194
(1.00) 		0.857
(1.00)
3p gain 18 (10%) 155 0.311
(1.00) 		0.678
(1.00) 		0.00209
(1.00) 		0.317
(1.00) 		0.907
(1.00) 		0.529
(1.00) 		0.705
(1.00)
3q gain 23 (13%) 150 0.285
(1.00) 		0.445
(1.00) 		0.00433
(1.00) 		0.364
(1.00) 		0.851
(1.00) 		0.33
(1.00) 		0.793
(1.00)
4p gain 17 (10%) 156 0.206
(1.00) 		0.0496
(1.00) 		0.821
(1.00) 		0.601
(1.00) 		0.927
(1.00) 		0.31
(1.00) 		0.0337
(1.00)
4q gain 13 (8%) 160 0.181
(1.00) 		0.0491
(1.00) 		0.776
(1.00) 		1
(1.00) 		0.966
(1.00) 		0.451
(1.00) 		0.0829
(1.00)
5p gain 19 (11%) 154 0.67
(1.00) 		0.271
(1.00) 		0.073
(1.00) 		0.805
(1.00) 		0.165
(1.00) 		0.633
(1.00) 		0.513
(1.00)
5q gain 7 (4%) 166 0.117
(1.00) 		0.125
(1.00) 		0.708
(1.00) 		0.988
(1.00) 		0.545
(1.00) 		0.584
(1.00)
6p gain 58 (34%) 115 0.192
(1.00) 		0.229
(1.00) 		0.052
(1.00) 		0.141
(1.00) 		0.648
(1.00) 		0.582
(1.00) 		0.463
(1.00)
6q gain 12 (7%) 161 0.95
(1.00) 		0.811
(1.00) 		0.633
(1.00) 		0.541
(1.00) 		0.186
(1.00) 		0.941
(1.00) 		0.47
(1.00)
7p gain 73 (42%) 100 0.122
(1.00) 		0.837
(1.00) 		0.322
(1.00) 		0.345
(1.00) 		0.0406
(1.00) 		0.146
(1.00) 		0.117
(1.00)
7q gain 74 (43%) 99 0.365
(1.00) 		0.534
(1.00) 		0.437
(1.00) 		0.876
(1.00) 		0.0506
(1.00) 		0.175
(1.00) 		0.0178
(1.00)
8p gain 35 (20%) 138 0.52
(1.00) 		0.736
(1.00) 		0.287
(1.00) 		0.34
(1.00) 		0.0464
(1.00) 		0.677
(1.00) 		0.515
(1.00)
8q gain 54 (31%) 119 0.424
(1.00) 		0.548
(1.00) 		0.326
(1.00) 		0.4
(1.00) 		0.159
(1.00) 		0.492
(1.00) 		0.717
(1.00)
9p gain 3 (2%) 170 0.0336
(1.00) 		0.731
(1.00) 		0.56
(1.00) 		0.997
(1.00) 		0.0276
(1.00) 		0.489
(1.00)
9q gain 3 (2%) 170 0.877
(1.00) 		1
(1.00) 		0.56
(1.00) 		0.997
(1.00) 		0.176
(1.00) 		0.936
(1.00)
11p gain 11 (6%) 162 0.993
(1.00) 		0.27
(1.00) 		0.741
(1.00) 		0.533
(1.00) 		0.966
(1.00) 		0.103
(1.00) 		0.809
(1.00)
11q gain 8 (5%) 165 0.928
(1.00) 		0.303
(1.00) 		0.674
(1.00) 		0.487
(1.00) 		0.983
(1.00) 		0.929
(1.00) 		0.667
(1.00)
12p gain 19 (11%) 154 0.44
(1.00) 		0.582
(1.00) 		0.411
(1.00) 		0.621
(1.00) 		0.165
(1.00) 		0.152
(1.00) 		0.142
(1.00)
12q gain 7 (4%) 166 0.935
(1.00) 		0.916
(1.00) 		0.856
(1.00) 		0.251
(1.00) 		0.988
(1.00) 		0.0172
(1.00) 		0.108
(1.00)
13q gain 30 (17%) 143 0.452
(1.00) 		0.904
(1.00) 		0.0144
(1.00) 		0.84
(1.00) 		0.577
(1.00) 		0.125
(1.00) 		0.106
(1.00)
14q gain 14 (8%) 159 0.565
(1.00) 		0.782
(1.00) 		1
(1.00) 		0.57
(1.00) 		0.952
(1.00) 		0.719
(1.00) 		0.894
(1.00)
15q gain 26 (15%) 147 0.614
(1.00) 		0.363
(1.00) 		0.776
(1.00) 		1
(1.00) 		0.825
(1.00) 		0.487
(1.00) 		0.933
(1.00)
16p gain 13 (8%) 160 0.204
(1.00) 		0.99
(1.00) 		0.256
(1.00) 		1
(1.00) 		0.944
(1.00) 		0.679
(1.00) 		0.517
(1.00)
16q gain 12 (7%) 161 0.359
(1.00) 		0.663
(1.00) 		0.451
(1.00) 		0.768
(1.00) 		0.952
(1.00) 		0.29
(1.00) 		0.727
(1.00)
17p gain 14 (8%) 159 0.879
(1.00) 		0.926
(1.00) 		0.405
(1.00) 		0.4
(1.00) 		0.228
(1.00) 		0.94
(1.00) 		0.13
(1.00)
17q gain 22 (13%) 151 0.0905
(1.00) 		0.051
(1.00) 		0.861
(1.00) 		0.252
(1.00) 		0.494
(1.00) 		0.598
(1.00) 		0.175
(1.00)
19p gain 11 (6%) 162 0.542
(1.00) 		0.313
(1.00) 		0.0869
(1.00) 		0.752
(1.00) 		0.966
(1.00) 		0.969
(1.00) 		0.0866
(1.00)
19q gain 15 (9%) 158 0.483
(1.00) 		0.107
(1.00) 		0.4
(1.00) 		0.0976
(1.00) 		0.936
(1.00) 		0.609
(1.00) 		0.146
(1.00)
20p gain 53 (31%) 120 0.727
(1.00) 		0.519
(1.00) 		0.554
(1.00) 		0.735
(1.00) 		0.159
(1.00) 		0.709
(1.00) 		0.646
(1.00)
20q gain 65 (38%) 108 0.749
(1.00) 		0.991
(1.00) 		0.554
(1.00) 		0.522
(1.00) 		0.086
(1.00) 		0.947
(1.00) 		0.612
(1.00)
21q gain 21 (12%) 152 0.0191
(1.00) 		0.918
(1.00) 		0.433
(1.00) 		0.474
(1.00) 		0.194
(1.00) 		0.335
(1.00) 		0.0289
(1.00)
22q gain 46 (27%) 127 0.49
(1.00) 		0.947
(1.00) 		0.0724
(1.00) 		0.292
(1.00) 		0.656
(1.00) 		0.0482
(1.00) 		0.0397
(1.00)
Xq gain 3 (2%) 170 0.0703
(1.00) 		0.291
(1.00) 		0.284
(1.00)
1p loss 13 (8%) 160 0.648
(1.00) 		0.71
(1.00) 		0.658
(1.00) 		1
(1.00) 		0.966
(1.00) 		0.173
(1.00) 		0.263
(1.00)
1q loss 6 (3%) 167 0.952
(1.00) 		0.455
(1.00) 		0.126
(1.00) 		0.678
(1.00) 		0.988
(1.00) 		0.523
(1.00) 		0.887
(1.00)
2p loss 15 (9%) 158 0.676
(1.00) 		0.802
(1.00) 		0.599
(1.00) 		1
(1.00) 		0.952
(1.00) 		0.974
(1.00) 		0.322
(1.00)
2q loss 14 (8%) 159 0.727
(1.00) 		0.432
(1.00) 		0.79
(1.00) 		0.4
(1.00) 		0.228
(1.00) 		0.91
(1.00) 		0.182
(1.00)
3p loss 12 (7%) 161 0.299
(1.00) 		0.263
(1.00) 		0.285
(1.00) 		1
(1.00) 		0.966
(1.00) 		0.206
(1.00) 		0.0474
(1.00)
3q loss 12 (7%) 161 0.302
(1.00) 		0.363
(1.00) 		0.31
(1.00) 		0.541
(1.00) 		0.966
(1.00) 		0.206
(1.00) 		0.361
(1.00)
4p loss 19 (11%) 154 0.964
(1.00) 		0.459
(1.00) 		0.284
(1.00) 		0.0256
(1.00) 		0.383
(1.00) 		0.888
(1.00) 		0.764
(1.00)
4q loss 18 (10%) 155 0.811
(1.00) 		0.532
(1.00) 		0.433
(1.00) 		0.0708
(1.00) 		0.000543
(0.286) 		0.755
(1.00) 		0.728
(1.00)
5p loss 23 (13%) 150 0.667
(1.00) 		0.513
(1.00) 		0.258
(1.00) 		1
(1.00) 		0.886
(1.00) 		0.947
(1.00) 		0.977
(1.00)
5q loss 37 (21%) 136 0.796
(1.00) 		0.623
(1.00) 		0.252
(1.00) 		0.705
(1.00) 		0.451
(1.00) 		0.678
(1.00) 		0.824
(1.00)
6p loss 17 (10%) 156 0.958
(1.00) 		0.998
(1.00) 		0.154
(1.00) 		1
(1.00) 		0.907
(1.00) 		0.86
(1.00) 		0.189
(1.00)
6q loss 69 (40%) 104 0.415
(1.00) 		0.0916
(1.00) 		0.0965
(1.00) 		1
(1.00) 		0.553
(1.00) 		0.776
(1.00) 		0.532
(1.00)
7p loss 3 (2%) 170 0.583
(1.00) 		0.291
(1.00) 		0.56
(1.00) 		0.997
(1.00) 		0.978
(1.00) 		0.381
(1.00)
7q loss 3 (2%) 170 0.583
(1.00) 		0.291
(1.00) 		0.56
(1.00) 		0.997
(1.00) 		0.978
(1.00) 		0.381
(1.00)
8p loss 22 (13%) 151 0.251
(1.00) 		0.917
(1.00) 		0.23
(1.00) 		1
(1.00) 		0.471
(1.00) 		0.579
(1.00) 		0.452
(1.00)
8q loss 3 (2%) 170 0.627
(1.00) 		0.475
(1.00) 		0.0565
(1.00) 		0.997
(1.00) 		0.349
(1.00) 		0.448
(1.00)
9p loss 100 (58%) 73 0.0303
(1.00) 		0.445
(1.00) 		0.0275
(1.00) 		0.753
(1.00) 		0.553
(1.00) 		0.0269
(1.00) 		0.0628
(1.00)
9q loss 75 (43%) 98 0.228
(1.00) 		0.0934
(1.00) 		0.0997
(1.00) 		0.0403
(1.00) 		0.235
(1.00) 		0.356
(1.00) 		0.026
(1.00)
10p loss 77 (45%) 96 0.108
(1.00) 		0.186
(1.00) 		0.195
(1.00) 		0.0604
(1.00) 		0.393
(1.00) 		0.18
(1.00) 		0.676
(1.00)
10q loss 84 (49%) 89 0.232
(1.00) 		0.00474
(1.00) 		0.135
(1.00) 		0.212
(1.00) 		0.184
(1.00) 		0.437
(1.00) 		0.732
(1.00)
11p loss 45 (26%) 128 0.732
(1.00) 		0.286
(1.00) 		0.433
(1.00) 		0.113
(1.00) 		0.0817
(1.00) 		0.263
(1.00) 		0.0406
(1.00)
11q loss 48 (28%) 125 0.907
(1.00) 		0.949
(1.00) 		0.312
(1.00) 		0.163
(1.00) 		0.112
(1.00) 		0.282
(1.00) 		0.0126
(1.00)
12p loss 10 (6%) 163 0.273
(1.00) 		0.787
(1.00) 		0.52
(1.00) 		0.513
(1.00) 		0.143
(1.00) 		0.246
(1.00) 		0.55
(1.00)
12q loss 19 (11%) 154 0.934
(1.00) 		0.956
(1.00) 		0.233
(1.00) 		0.216
(1.00) 		0.165
(1.00) 		0.484
(1.00) 		0.765
(1.00)
13q loss 26 (15%) 147 0.7
(1.00) 		0.645
(1.00) 		0.0837
(1.00) 		0.67
(1.00) 		0.00556
(1.00) 		0.0972
(1.00) 		0.485
(1.00)
14q loss 42 (24%) 131 0.895
(1.00) 		0.46
(1.00) 		0.754
(1.00) 		0.718
(1.00) 		0.102
(1.00) 		0.426
(1.00) 		0.46
(1.00)
15q loss 11 (6%) 162 0.475
(1.00) 		0.294
(1.00) 		0.178
(1.00) 		0.752
(1.00) 		0.143
(1.00) 		0.466
(1.00) 		0.876
(1.00)
16p loss 14 (8%) 159 0.352
(1.00) 		0.375
(1.00) 		0.532
(1.00) 		0.4
(1.00) 		0.96
(1.00) 		0.801
(1.00) 		0.248
(1.00)
16q loss 31 (18%) 142 0.129
(1.00) 		0.768
(1.00) 		0.463
(1.00) 		0.689
(1.00) 		0.42
(1.00) 		0.853
(1.00) 		0.221
(1.00)
17p loss 38 (22%) 135 0.942
(1.00) 		0.537
(1.00) 		0.206
(1.00) 		0.575
(1.00) 		0.554
(1.00) 		0.722
(1.00) 		0.728
(1.00)
17q loss 17 (10%) 156 0.307
(1.00) 		0.849
(1.00) 		0.729
(1.00) 		1
(1.00) 		0.11
(1.00) 		0.171
(1.00) 		0.629
(1.00)
18p loss 35 (20%) 138 0.895
(1.00) 		0.523
(1.00) 		0.146
(1.00) 		0.568
(1.00) 		0.71
(1.00) 		0.129
(1.00) 		0.218
(1.00)
18q loss 33 (19%) 140 0.882
(1.00) 		0.447
(1.00) 		0.165
(1.00) 		0.693
(1.00) 		0.618
(1.00) 		0.304
(1.00) 		0.137
(1.00)
19p loss 15 (9%) 158 0.771
(1.00) 		0.393
(1.00) 		0.599
(1.00) 		0.0266
(1.00) 		0.0853
(1.00) 		0.614
(1.00) 		0.263
(1.00)
19q loss 16 (9%) 157 0.539
(1.00) 		0.708
(1.00) 		0.0387
(1.00) 		0.178
(1.00) 		0.0447
(1.00) 		0.431
(1.00) 		0.485
(1.00)
20p loss 7 (4%) 166 0.219
(1.00) 		0.342
(1.00) 		0.238
(1.00) 		0.708
(1.00) 		0.0379
(1.00) 		0.874
(1.00) 		0.658
(1.00)
21q loss 21 (12%) 152 0.868
(1.00) 		0.887
(1.00) 		0.857
(1.00) 		0.812
(1.00) 		0.875
(1.00) 		0.726
(1.00) 		0.137
(1.00)
22q loss 13 (8%) 160 0.344
(1.00) 		0.668
(1.00) 		0.346
(1.00) 		0.568
(1.00) 		0.27
(1.00) 		0.992
(1.00) 		0.325
(1.00)
Xq loss 6 (3%) 167 0.797
(1.00) 		0.636
(1.00) 		0.595
(1.00) 		0.0329
(1.00) 		0.991
(1.00) 		0.983
(1.00) 		0.504
(1.00)
'18p gain mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 2.58e-05 (Chi-square test), Q value = 0.014

Table S1.  Gene #30: '18p gain mutation analysis' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients I OR II NOS STAGE I STAGE IA STAGE IB STAGE II STAGE IIA STAGE IIB STAGE IIC STAGE III STAGE IIIA STAGE IIIB STAGE IIIC STAGE IV
ALL 4 17 10 14 19 8 10 8 9 6 18 23 6
18P GAIN MUTATED 2 3 0 0 2 0 0 6 1 3 2 3 0
18P GAIN WILD-TYPE 2 14 10 14 17 8 10 2 8 3 16 20 6

Figure S1.  Get High-res Image Gene #30: '18p gain mutation analysis' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

'18q gain mutation analysis' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.16e-07 (Chi-square test), Q value = 6.2e-05

Table S2.  Gene #31: '18q gain mutation analysis' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

nPatients I OR II NOS STAGE I STAGE IA STAGE IB STAGE II STAGE IIA STAGE IIB STAGE IIC STAGE III STAGE IIIA STAGE IIIB STAGE IIIC STAGE IV
ALL 4 17 10 14 19 8 10 8 9 6 18 23 6
18Q GAIN MUTATED 2 1 0 0 0 0 0 5 0 2 0 2 0
18Q GAIN WILD-TYPE 2 16 10 14 19 8 10 3 9 4 18 21 6

Figure S2.  Get High-res Image Gene #31: '18q gain mutation analysis' versus Clinical Feature #8: 'NEOPLASM.DISEASESTAGE'

Methods & Data
Input

  • Mutation data file = broad_values_by_arm.mutsig.cluster.txt

  • Clinical data file = SKCM-All_Metastatic.clin.merged.picked.txt

  • Number of patients = 173

  • Number of significantly arm-level cnvs = 77

  • Number of selected clinical features = 8

  • 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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

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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