Correlation between copy number variations of arm-level result and selected clinical features
Skin Cutaneous Melanoma (Metastatic)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1TD9VDS
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between copy number variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1TD9VDS
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 180 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 0 (0%) 158 0.616
(1.00) 		0.0715
(1.00) 		0.823
(1.00) 		0.351
(1.00) 		0.497
(1.00) 		0.522
(1.00) 		1.13e-05
(0.00605)
18q gain 0 (0%) 168 0.346
(1.00) 		0.496
(1.00) 		0.2
(1.00) 		0.542
(1.00) 		0.963
(1.00) 		0.578
(1.00) 		3.76e-08
(2.02e-05)
1p gain 0 (0%) 158 0.159
(1.00) 		0.148
(1.00) 		0.398
(1.00) 		0.495
(1.00) 		0.874
(1.00) 		0.413
(1.00) 		0.0129
(1.00)
1q gain 0 (0%) 118 0.613
(1.00) 		0.948
(1.00) 		0.161
(1.00) 		0.872
(1.00) 		0.636
(1.00) 		0.326
(1.00) 		0.6
(1.00)
2p gain 0 (0%) 162 0.41
(1.00) 		0.035
(1.00) 		0.662
(1.00) 		0.201
(1.00) 		0.915
(1.00) 		0.133
(1.00) 		0.856
(1.00)
2q gain 0 (0%) 163 0.655
(1.00) 		0.0626
(1.00) 		0.372
(1.00) 		0.447
(1.00) 		0.924
(1.00) 		0.23
(1.00) 		0.833
(1.00)
3p gain 0 (0%) 162 0.788
(1.00) 		0.692
(1.00) 		0.00218
(1.00) 		0.32
(1.00) 		0.915
(1.00) 		0.554
(1.00) 		0.698
(1.00)
3q gain 0 (0%) 157 0.414
(1.00) 		0.459
(1.00) 		0.00541
(1.00) 		0.367
(1.00) 		0.862
(1.00) 		0.364
(1.00) 		0.767
(1.00)
4p gain 0 (0%) 162 0.511
(1.00) 		0.0237
(1.00) 		0.662
(1.00) 		0.32
(1.00) 		0.924
(1.00) 		0.488
(1.00) 		0.0383
(1.00)
4q gain 0 (0%) 166 0.605
(1.00) 		0.0228
(1.00) 		0.855
(1.00) 		0.78
(1.00) 		0.963
(1.00) 		0.678
(1.00) 		0.0894
(1.00)
5p gain 0 (0%) 160 0.0441
(1.00) 		0.161
(1.00) 		0.224
(1.00) 		0.629
(1.00) 		0.171
(1.00) 		0.568
(1.00) 		0.52
(1.00)
5q gain 0 (0%) 171 0.381
(1.00) 		0.0688
(1.00) 		0.309
(1.00) 		0.737
(1.00) 		0.98
(1.00) 		0.54
(1.00) 		0.389
(1.00)
6p gain 0 (0%) 120 0.968
(1.00) 		0.336
(1.00) 		0.0485
(1.00) 		0.146
(1.00) 		0.648
(1.00) 		0.615
(1.00) 		0.431
(1.00)
6q gain 0 (0%) 165 0.472
(1.00) 		0.94
(1.00) 		0.0665
(1.00) 		0.585
(1.00) 		0.052
(1.00) 		0.863
(1.00) 		0.82
(1.00)
7p gain 0 (0%) 104 0.698
(1.00) 		0.72
(1.00) 		0.24
(1.00) 		0.444
(1.00) 		0.0409
(1.00) 		0.211
(1.00) 		0.183
(1.00)
7q gain 0 (0%) 103 0.954
(1.00) 		0.645
(1.00) 		0.325
(1.00) 		1
(1.00) 		0.0505
(1.00) 		0.252
(1.00) 		0.0328
(1.00)
8p gain 0 (0%) 140 0.873
(1.00) 		0.794
(1.00) 		0.328
(1.00) 		0.366
(1.00) 		0.0651
(1.00) 		0.69
(1.00) 		0.433
(1.00)
8q gain 0 (0%) 120 0.853
(1.00) 		0.575
(1.00) 		0.288
(1.00) 		0.331
(1.00) 		0.181
(1.00) 		0.577
(1.00) 		0.725
(1.00)
9p gain 0 (0%) 176 0.83
(1.00) 		0.147
(1.00) 		0.453
(1.00) 		0.643
(1.00) 		0.995
(1.00) 		0.138
(1.00) 		0.307
(1.00)
9q gain 0 (0%) 176 0.966
(1.00) 		0.933
(1.00) 		0.615
(1.00) 		0.643
(1.00) 		0.995
(1.00) 		0.316
(1.00) 		0.681
(1.00)
11p gain 0 (0%) 169 0.903
(1.00) 		0.263
(1.00) 		0.745
(1.00) 		0.533
(1.00) 		0.969
(1.00) 		0.119
(1.00) 		0.807
(1.00)
11q gain 0 (0%) 172 0.39
(1.00) 		0.297
(1.00) 		0.76
(1.00) 		0.486
(1.00) 		0.985
(1.00) 		0.944
(1.00) 		0.678
(1.00)
12p gain 0 (0%) 159 0.963
(1.00) 		0.64
(1.00) 		0.629
(1.00) 		1
(1.00) 		0.199
(1.00) 		0.186
(1.00) 		0.202
(1.00)
12q gain 0 (0%) 172 0.746
(1.00) 		0.814
(1.00) 		0.876
(1.00) 		0.486
(1.00) 		0.985
(1.00) 		0.0292
(1.00) 		0.142
(1.00)
13q gain 0 (0%) 149 0.513
(1.00) 		0.769
(1.00) 		0.0301
(1.00) 		0.84
(1.00) 		0.576
(1.00) 		0.26
(1.00) 		0.108
(1.00)
14q gain 0 (0%) 166 0.726
(1.00) 		0.77
(1.00) 		1
(1.00) 		0.571
(1.00) 		0.956
(1.00) 		0.72
(1.00) 		0.873
(1.00)
15q gain 0 (0%) 154 0.824
(1.00) 		0.351
(1.00) 		0.811
(1.00) 		1
(1.00) 		0.839
(1.00) 		0.424
(1.00) 		0.932
(1.00)
16p gain 0 (0%) 164 0.795
(1.00) 		0.794
(1.00) 		0.195
(1.00) 		1
(1.00) 		0.924
(1.00) 		0.834
(1.00) 		0.37
(1.00)
16q gain 0 (0%) 167 0.779
(1.00) 		0.381
(1.00) 		0.241
(1.00) 		1
(1.00) 		0.949
(1.00) 		0.309
(1.00) 		0.611
(1.00)
17p gain 0 (0%) 165 0.637
(1.00) 		0.962
(1.00) 		0.375
(1.00) 		0.273
(1.00) 		0.247
(1.00) 		0.931
(1.00) 		0.0952
(1.00)
17q gain 0 (0%) 156 0.301
(1.00) 		0.0634
(1.00) 		0.764
(1.00) 		0.264
(1.00) 		0.517
(1.00) 		0.627
(1.00) 		0.186
(1.00)
19p gain 0 (0%) 168 0.578
(1.00) 		0.17
(1.00) 		0.252
(1.00) 		0.542
(1.00) 		0.963
(1.00) 		0.942
(1.00) 		0.0884
(1.00)
19q gain 0 (0%) 164 0.574
(1.00) 		0.054
(1.00) 		0.547
(1.00) 		0.0589
(1.00) 		0.933
(1.00) 		0.646
(1.00) 		0.156
(1.00)
20p gain 0 (0%) 125 0.569
(1.00) 		0.478
(1.00) 		0.602
(1.00) 		0.74
(1.00) 		0.158
(1.00) 		0.798
(1.00) 		0.603
(1.00)
20q gain 0 (0%) 113 0.166
(1.00) 		0.946
(1.00) 		0.647
(1.00) 		0.532
(1.00) 		0.0828
(1.00) 		0.969
(1.00) 		0.604
(1.00)
21q gain 0 (0%) 159 0.75
(1.00) 		0.901
(1.00) 		0.435
(1.00) 		0.476
(1.00) 		0.171
(1.00) 		0.3
(1.00) 		0.0303
(1.00)
22q gain 0 (0%) 132 0.151
(1.00) 		0.887
(1.00) 		0.0568
(1.00) 		0.3
(1.00) 		0.659
(1.00) 		0.061
(1.00) 		0.0431
(1.00)
Xq gain 0 (0%) 177 0.695
(1.00) 		0.0702
(1.00) 		0.295
(1.00) 		0.283
(1.00)
1p loss 0 (0%) 166 0.128
(1.00) 		0.801
(1.00) 		0.583
(1.00) 		0.78
(1.00) 		0.963
(1.00) 		0.322
(1.00) 		0.314
(1.00)
1q loss 0 (0%) 174 0.904
(1.00) 		0.444
(1.00) 		0.128
(1.00) 		0.679
(1.00) 		0.989
(1.00) 		0.578
(1.00) 		0.893
(1.00)
2p loss 0 (0%) 165 0.12
(1.00) 		0.79
(1.00) 		0.602
(1.00) 		1
(1.00) 		0.956
(1.00) 		0.971
(1.00) 		0.286
(1.00)
2q loss 0 (0%) 166 0.199
(1.00) 		0.425
(1.00) 		0.739
(1.00) 		0.403
(1.00) 		0.207
(1.00) 		0.913
(1.00) 		0.157
(1.00)
3p loss 0 (0%) 167 0.325
(1.00) 		0.17
(1.00) 		0.303
(1.00) 		1
(1.00) 		0.963
(1.00) 		0.383
(1.00) 		0.0752
(1.00)
3q loss 0 (0%) 167 0.329
(1.00) 		0.557
(1.00) 		0.281
(1.00) 		0.57
(1.00) 		0.963
(1.00) 		0.383
(1.00) 		0.439
(1.00)
4p loss 0 (0%) 160 0.937
(1.00) 		0.436
(1.00) 		0.343
(1.00) 		0.0517
(1.00) 		0.392
(1.00) 		0.96
(1.00) 		0.6
(1.00)
4q loss 0 (0%) 161 0.946
(1.00) 		0.508
(1.00) 		0.465
(1.00) 		0.0848
(1.00) 		0.000662
(0.354) 		0.896
(1.00) 		0.643
(1.00)
5p loss 0 (0%) 155 0.588
(1.00) 		0.521
(1.00) 		0.246
(1.00) 		1
(1.00) 		0.874
(1.00) 		0.985
(1.00) 		0.873
(1.00)
5q loss 0 (0%) 141 0.433
(1.00) 		0.627
(1.00) 		0.201
(1.00) 		0.714
(1.00) 		0.466
(1.00) 		0.896
(1.00) 		0.859
(1.00)
6p loss 0 (0%) 165 0.448
(1.00) 		0.905
(1.00) 		0.0912
(1.00) 		1
(1.00) 		0.933
(1.00) 		0.859
(1.00) 		0.746
(1.00)
6q loss 0 (0%) 112 0.696
(1.00) 		0.137
(1.00) 		0.162
(1.00) 		0.876
(1.00) 		0.983
(1.00) 		0.634
(1.00) 		0.434
(1.00)
7p loss 0 (0%) 177 0.0683
(1.00) 		0.58
(1.00) 		0.295
(1.00) 		0.561
(1.00) 		0.997
(1.00) 		0.973
(1.00) 		0.391
(1.00)
7q loss 0 (0%) 177 0.0683
(1.00) 		0.58
(1.00) 		0.295
(1.00) 		0.561
(1.00) 		0.997
(1.00) 		0.973
(1.00) 		0.391
(1.00)
8p loss 0 (0%) 158 0.995
(1.00) 		0.933
(1.00) 		0.26
(1.00) 		1
(1.00) 		0.45
(1.00) 		0.528
(1.00) 		0.487
(1.00)
8q loss 0 (0%) 177 0.333
(1.00) 		0.623
(1.00) 		0.484
(1.00) 		0.0573
(1.00) 		0.997
(1.00) 		0.31
(1.00) 		0.463
(1.00)
9p loss 0 (0%) 75 0.329
(1.00) 		0.358
(1.00) 		0.0331
(1.00) 		0.538
(1.00) 		0.562
(1.00) 		0.0343
(1.00) 		0.0392
(1.00)
9q loss 0 (0%) 102 0.737
(1.00) 		0.0769
(1.00) 		0.126
(1.00) 		0.0211
(1.00) 		0.236
(1.00) 		0.289
(1.00) 		0.0153
(1.00)
10p loss 0 (0%) 103 0.15
(1.00) 		0.238
(1.00) 		0.282
(1.00) 		0.0659
(1.00) 		0.379
(1.00) 		0.262
(1.00) 		0.767
(1.00)
10q loss 0 (0%) 92 0.579
(1.00) 		0.00647
(1.00) 		0.116
(1.00) 		0.169
(1.00) 		0.187
(1.00) 		0.405
(1.00) 		0.692
(1.00)
11p loss 0 (0%) 132 0.0503
(1.00) 		0.201
(1.00) 		0.411
(1.00) 		0.0837
(1.00) 		0.0938
(1.00) 		0.434
(1.00) 		0.0341
(1.00)
11q loss 0 (0%) 126 0.0311
(1.00) 		0.882
(1.00) 		0.397
(1.00) 		0.0993
(1.00) 		0.157
(1.00) 		0.462
(1.00) 		0.0149
(1.00)
12p loss 0 (0%) 168 0.717
(1.00) 		0.762
(1.00) 		0.413
(1.00) 		0.542
(1.00) 		0.207
(1.00) 		0.312
(1.00) 		0.73
(1.00)
12q loss 0 (0%) 160 0.751
(1.00) 		0.748
(1.00) 		0.117
(1.00) 		0.333
(1.00) 		0.171
(1.00) 		0.439
(1.00) 		0.529
(1.00)
13q loss 0 (0%) 153 0.983
(1.00) 		0.571
(1.00) 		0.162
(1.00) 		0.833
(1.00) 		0.00554
(1.00) 		0.115
(1.00) 		0.625
(1.00)
14q loss 0 (0%) 136 0.761
(1.00) 		0.588
(1.00) 		0.684
(1.00) 		0.726
(1.00) 		0.103
(1.00) 		0.603
(1.00) 		0.492
(1.00)
15q loss 0 (0%) 169 0.621
(1.00) 		0.3
(1.00) 		0.15
(1.00) 		0.753
(1.00) 		0.126
(1.00) 		0.513
(1.00) 		0.885
(1.00)
16p loss 0 (0%) 166 0.312
(1.00) 		0.369
(1.00) 		0.536
(1.00) 		0.403
(1.00) 		0.963
(1.00) 		0.767
(1.00) 		0.211
(1.00)
16q loss 0 (0%) 149 0.0164
(1.00) 		0.75
(1.00) 		0.532
(1.00) 		0.692
(1.00) 		0.391
(1.00) 		0.868
(1.00) 		0.184
(1.00)
17p loss 0 (0%) 142 0.452
(1.00) 		0.521
(1.00) 		0.216
(1.00) 		0.577
(1.00) 		0.516
(1.00) 		0.687
(1.00) 		0.488
(1.00)
17q loss 0 (0%) 163 0.114
(1.00) 		0.861
(1.00) 		0.773
(1.00) 		0.8
(1.00) 		0.0931
(1.00) 		0.143
(1.00) 		0.606
(1.00)
18p loss 0 (0%) 145 0.515
(1.00) 		0.51
(1.00) 		0.158
(1.00) 		0.7
(1.00) 		0.732
(1.00) 		0.128
(1.00) 		0.189
(1.00)
18q loss 0 (0%) 147 0.524
(1.00) 		0.436
(1.00) 		0.179
(1.00) 		0.695
(1.00) 		0.613
(1.00) 		0.322
(1.00) 		0.137
(1.00)
19p loss 0 (0%) 165 0.4
(1.00) 		0.385
(1.00) 		0.602
(1.00) 		0.0274
(1.00) 		0.0712
(1.00) 		0.659
(1.00) 		0.271
(1.00)
19q loss 0 (0%) 164 0.92
(1.00) 		0.696
(1.00) 		0.0321
(1.00) 		0.179
(1.00) 		0.0359
(1.00) 		0.502
(1.00) 		0.496
(1.00)
20p loss 0 (0%) 172 0.712
(1.00) 		0.456
(1.00) 		0.187
(1.00) 		0.486
(1.00) 		0.0564
(1.00) 		0.957
(1.00) 		0.715
(1.00)
21q loss 0 (0%) 158 0.947
(1.00) 		0.915
(1.00) 		0.786
(1.00) 		0.82
(1.00) 		0.874
(1.00) 		0.728
(1.00) 		0.113
(1.00)
22q loss 0 (0%) 167 0.963
(1.00) 		0.678
(1.00) 		0.303
(1.00) 		0.57
(1.00) 		0.247
(1.00) 		0.993
(1.00) 		0.322
(1.00)
Xq loss 0 (0%) 174 0.473
(1.00) 		0.625
(1.00) 		0.503
(1.00) 		0.0337
(1.00) 		0.992
(1.00) 		0.985
(1.00) 		0.474
(1.00)
'18p gain' versus 'NEOPLASM.DISEASESTAGE'

P value = 1.13e-05 (Chi-square test), Q value = 0.006

Table S1.  Gene #30: '18p gain' 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 18 10 15 19 9 10 8 10 6 19 25 6
18P GAIN CNV 2 3 0 0 2 0 0 6 1 3 2 3 0
18P GAIN WILD-TYPE 2 15 10 15 17 9 10 2 9 3 17 22 6

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

'18q gain' versus 'NEOPLASM.DISEASESTAGE'

P value = 3.76e-08 (Chi-square test), Q value = 2e-05

Table S2.  Gene #31: '18q gain' 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 18 10 15 19 9 10 8 10 6 19 25 6
18Q GAIN CNV 2 1 0 0 0 0 0 5 0 2 0 2 0
18Q GAIN WILD-TYPE 2 17 10 15 19 9 10 3 10 4 19 23 6

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

Methods & Data
Input

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

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

  • Number of patients = 180

  • 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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