Correlation between copy number variations of arm-level result and selected clinical features
Pheochromocytoma and Paraganglioma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
doi:10.7908/C15T3JXR
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between copy number variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C15T3JXR
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 70 arm-level events and 9 clinical features across 162 patients, 4 significant findings detected with Q value < 0.25.

  • 1q gain cnv correlated to 'RADIATION_THERAPY'.

  • 20q gain cnv correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

  • 12p loss cnv correlated to 'Time to Death'.

  • 16p loss cnv correlated to 'Time to Death'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 70 arm-level events and 9 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 4 significant findings detected.

Clinical
Features 		Time
to
Death 		YEARS
TO
BIRTH 		TUMOR
TISSUE
SITE 		GENDER RADIATION
THERAPY 		KARNOFSKY
PERFORMANCE
SCORE 		HISTOLOGICAL
TYPE 		NUMBER
OF
LYMPH
NODES 		RACE
nCNV (%) nWild-Type logrank test Wilcoxon-test Fisher's exact test Fisher's exact test Fisher's exact test Wilcoxon-test Fisher's exact test Wilcoxon-test Fisher's exact test
1q gain 19 (12%) 143 0.649
(1.00) 		0.115
(1.00) 		0.329
(1.00) 		0.328
(1.00) 		0.00068
(0.107) 		0.784
(1.00) 		0.776
(1.00) 		0.292
(1.00) 		0.857
(1.00)
20q gain 10 (6%) 152 0.517
(1.00) 		0.333
(1.00) 		0.213
(1.00) 		0.756
(1.00) 		1
(1.00) 		0.000306
(0.0642) 		0.807
(1.00) 		1
(1.00)
12p loss 3 (2%) 159 2.26e-05
(0.0143) 		0.0409
(0.927) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
16p loss 9 (6%) 153 6.78e-05
(0.0214) 		0.124
(1.00) 		0.655
(1.00) 		0.733
(1.00) 		0.0259
(0.849) 		0.317
(1.00) 		0.722
(1.00)
1p gain 6 (4%) 156 0.473
(1.00) 		0.546
(1.00) 		1
(1.00) 		0.0938
(1.00) 		0.176
(1.00) 		0.763
(1.00) 		0.67
(1.00) 		1
(1.00)
2p gain 6 (4%) 156 0.612
(1.00) 		0.968
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.668
(1.00) 		0.231
(1.00)
4p gain 4 (2%) 158 0.667
(1.00) 		0.339
(1.00) 		1
(1.00) 		0.332
(1.00) 		1
(1.00) 		1
(1.00) 		0.21
(1.00)
4q gain 3 (2%) 159 0.763
(1.00) 		0.305
(1.00) 		1
(1.00) 		0.593
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
5p gain 11 (7%) 151 0.503
(1.00) 		0.225
(1.00) 		0.214
(1.00) 		0.756
(1.00) 		1
(1.00) 		0.807
(1.00) 		0.671
(1.00) 		1
(1.00)
5q gain 7 (4%) 155 0.588
(1.00) 		0.863
(1.00) 		0.605
(1.00) 		0.127
(1.00) 		1
(1.00) 		0.799
(1.00) 		1
(1.00) 		1
(1.00)
6p gain 14 (9%) 148 0.509
(1.00) 		0.0132
(0.614) 		0.467
(1.00) 		1
(1.00) 		1
(1.00) 		0.33
(1.00) 		0.519
(1.00) 		0.822
(1.00)
6q gain 8 (5%) 154 0.628
(1.00) 		0.00866
(0.545) 		0.353
(1.00) 		0.728
(1.00) 		1
(1.00) 		0.0563
(1.00) 		1
(1.00) 		0.46
(1.00)
7p gain 27 (17%) 135 0.325
(1.00) 		0.694
(1.00) 		0.171
(1.00) 		0.53
(1.00) 		0.59
(1.00) 		0.503
(1.00) 		0.483
(1.00) 		0.617
(1.00)
7q gain 21 (13%) 141 0.4
(1.00) 		0.778
(1.00) 		1
(1.00) 		0.158
(1.00) 		1
(1.00) 		0.886
(1.00) 		1
(1.00) 		1
(1.00)
8p gain 9 (6%) 153 0.588
(1.00) 		0.151
(1.00) 		1
(1.00) 		0.733
(1.00) 		1
(1.00) 		0.323
(1.00) 		0.605
(1.00) 		1
(1.00)
8q gain 13 (8%) 149 0.315
(1.00) 		0.851
(1.00) 		0.47
(1.00) 		0.259
(1.00) 		1
(1.00) 		0.247
(1.00) 		0.503
(1.00) 		0.343
(1.00)
9p gain 4 (2%) 158 0.736
(1.00) 		0.742
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.496
(1.00)
9q gain 3 (2%) 159 0.763
(1.00) 		0.374
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.406
(1.00)
10p gain 12 (7%) 150 0.545
(1.00) 		0.972
(1.00) 		0.129
(1.00) 		1
(1.00) 		1
(1.00) 		0.468
(1.00) 		0.76
(1.00)
10q gain 10 (6%) 152 0.581
(1.00) 		0.646
(1.00) 		0.213
(1.00) 		0.514
(1.00) 		1
(1.00) 		0.806
(1.00) 		1
(1.00)
11p gain 5 (3%) 157 0.687
(1.00) 		0.611
(1.00) 		0.588
(1.00) 		0.377
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
12p gain 11 (7%) 151 0.517
(1.00) 		0.266
(1.00) 		0.214
(1.00) 		1
(1.00) 		1
(1.00) 		0.529
(1.00) 		0.668
(1.00) 		0.763
(1.00)
12q gain 14 (9%) 148 0.468
(1.00) 		0.661
(1.00) 		0.131
(1.00) 		1
(1.00) 		1
(1.00) 		0.33
(1.00) 		0.358
(1.00) 		0.818
(1.00)
13q gain 9 (6%) 153 0.596
(1.00) 		0.829
(1.00) 		1
(1.00) 		0.733
(1.00) 		1
(1.00) 		0.529
(1.00) 		1
(1.00) 		1
(1.00)
14q gain 4 (2%) 158 0.00695
(0.545) 		0.901
(1.00) 		1
(1.00) 		0.332
(1.00) 		1
(1.00) 		1
(1.00) 		0.5
(1.00)
15q gain 14 (9%) 148 0.481
(1.00) 		0.406
(1.00) 		0.131
(1.00) 		0.784
(1.00) 		1
(1.00) 		0.602
(1.00) 		0.361
(1.00) 		0.248
(1.00)
16p gain 6 (4%) 156 0.641
(1.00) 		0.327
(1.00) 		1
(1.00) 		0.689
(1.00) 		1
(1.00) 		0.671
(1.00) 		0.649
(1.00)
16q gain 6 (4%) 156 0.0652
(1.00) 		0.0753
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.671
(1.00) 		0.65
(1.00)
17q gain 6 (4%) 156 0.346
(1.00) 		0.546
(1.00) 		1
(1.00) 		0.0081
(0.545) 		0.0112
(0.598) 		0.429
(1.00) 		1
(1.00)
18p gain 8 (5%) 154 0.564
(1.00) 		0.954
(1.00) 		0.353
(1.00) 		0.471
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
18q gain 10 (6%) 152 0.527
(1.00) 		0.611
(1.00) 		0.213
(1.00) 		1
(1.00) 		1
(1.00) 		0.127
(1.00) 		0.806
(1.00) 		1
(1.00)
19p gain 20 (12%) 142 0.706
(1.00) 		0.019
(0.704) 		0.203
(1.00) 		0.638
(1.00) 		0.473
(1.00) 		0.646
(1.00) 		0.489
(1.00) 		1
(1.00)
19q gain 14 (9%) 148 0.469
(1.00) 		0.0235
(0.821) 		0.131
(1.00) 		1
(1.00) 		1
(1.00) 		0.602
(1.00) 		0.36
(1.00) 		0.82
(1.00)
20p gain 12 (7%) 150 0.503
(1.00) 		0.294
(1.00) 		0.693
(1.00) 		1
(1.00) 		1
(1.00) 		0.00276
(0.348) 		0.689
(1.00) 		0.606
(1.00)
21q gain 3 (2%) 159 0.764
(1.00) 		0.0182
(0.704) 		1
(1.00) 		0.593
(1.00) 		1
(1.00) 		1
(1.00) 		0.404
(1.00)
22q gain 3 (2%) 159 0.763
(1.00) 		0.543
(1.00) 		1
(1.00) 		0.593
(1.00) 		1
(1.00) 		1
(1.00) 		0.402
(1.00)
xp gain 6 (4%) 156 0.622
(1.00) 		0.842
(1.00) 		0.591
(1.00) 		0.221
(1.00) 		1
(1.00) 		1
(1.00) 		0.339
(1.00)
xq gain 5 (3%) 157 0.659
(1.00) 		0.958
(1.00) 		0.588
(1.00) 		0.377
(1.00) 		1
(1.00) 		1
(1.00) 		0.58
(1.00)
1p loss 97 (60%) 65 0.206
(1.00) 		0.828
(1.00) 		0.833
(1.00) 		0.631
(1.00) 		0.649
(1.00) 		0.744
(1.00) 		0.852
(1.00) 		0.654
(1.00) 		0.257
(1.00)
1q loss 25 (15%) 137 0.39
(1.00) 		0.858
(1.00) 		0.387
(1.00) 		0.282
(1.00) 		1
(1.00) 		0.73
(1.00) 		0.194
(1.00) 		0.143
(1.00)
2p loss 10 (6%) 152 0.628
(1.00) 		0.636
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.529
(1.00) 		0.504
(1.00) 		0.403
(1.00)
2q loss 13 (8%) 149 0.476
(1.00) 		0.995
(1.00) 		0.0114
(0.598) 		0.259
(1.00) 		1
(1.00) 		0.799
(1.00) 		0.0331
(0.906) 		0.53
(1.00)
3p loss 60 (37%) 102 0.563
(1.00) 		0.241
(1.00) 		0.286
(1.00) 		0.327
(1.00) 		0.359
(1.00) 		0.347
(1.00) 		0.463
(1.00) 		0.737
(1.00) 		0.113
(1.00)
3q loss 87 (54%) 75 0.323
(1.00) 		0.146
(1.00) 		0.835
(1.00) 		0.753
(1.00) 		1
(1.00) 		0.418
(1.00) 		0.819
(1.00) 		0.535
(1.00) 		0.965
(1.00)
4p loss 11 (7%) 151 0.612
(1.00) 		0.823
(1.00) 		0.691
(1.00) 		0.551
(1.00) 		1
(1.00) 		0.17
(1.00) 		1
(1.00) 		1
(1.00)
4q loss 10 (6%) 152 0.598
(1.00) 		0.989
(1.00) 		0.213
(1.00) 		0.514
(1.00) 		1
(1.00) 		0.17
(1.00) 		0.806
(1.00) 		1
(1.00)
5p loss 5 (3%) 157 0.774
(1.00) 		0.981
(1.00) 		0.588
(1.00) 		0.661
(1.00) 		1
(1.00) 		1
(1.00) 		0.58
(1.00)
5q loss 7 (4%) 155 0.691
(1.00) 		0.751
(1.00) 		0.605
(1.00) 		0.703
(1.00) 		1
(1.00) 		1
(1.00) 		0.652
(1.00) 		0.401
(1.00)
6q loss 18 (11%) 144 0.608
(1.00) 		0.681
(1.00) 		0.0445
(0.927) 		0.621
(1.00) 		1
(1.00) 		0.474
(1.00) 		0.217
(1.00) 		1
(1.00) 		0.849
(1.00)
7q loss 7 (4%) 155 0.0822
(1.00) 		0.607
(1.00) 		1
(1.00) 		0.703
(1.00) 		1
(1.00) 		0.574
(1.00) 		0.728
(1.00) 		0.0292
(0.876)
8p loss 21 (13%) 141 0.229
(1.00) 		0.225
(1.00) 		0.129
(1.00) 		0.249
(1.00) 		0.51
(1.00) 		0.707
(1.00) 		0.115
(1.00) 		0.78
(1.00)
8q loss 12 (7%) 150 0.313
(1.00) 		0.567
(1.00) 		0.693
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
9p loss 11 (7%) 151 0.0269
(0.849) 		0.704
(1.00) 		1
(1.00) 		1
(1.00) 		0.0385
(0.927) 		0.005
(0.525) 		0.422
(1.00) 		1
(1.00)
9q loss 12 (7%) 150 0.0544
(1.00) 		0.248
(1.00) 		1
(1.00) 		0.772
(1.00) 		0.0456
(0.927) 		0.577
(1.00) 		0.652
(1.00) 		0.779
(1.00)
11p loss 54 (33%) 108 0.55
(1.00) 		0.919
(1.00) 		0.511
(1.00) 		0.316
(1.00) 		0.663
(1.00) 		0.682
(1.00) 		0.568
(1.00) 		0.133
(1.00) 		0.598
(1.00)
11q loss 40 (25%) 122 0.89
(1.00) 		0.712
(1.00) 		0.472
(1.00) 		0.856
(1.00) 		0.332
(1.00) 		0.694
(1.00) 		0.543
(1.00) 		0.2
(1.00) 		1
(1.00)
13q loss 8 (5%) 154 0.594
(1.00) 		0.951
(1.00) 		0.353
(1.00) 		1
(1.00) 		1
(1.00) 		0.805
(1.00) 		1
(1.00) 		0.315
(1.00)
14q loss 20 (12%) 142 0.307
(1.00) 		0.311
(1.00) 		0.531
(1.00) 		0.811
(1.00) 		0.492
(1.00) 		0.627
(1.00) 		0.554
(1.00) 		0.669
(1.00)
15q loss 3 (2%) 159 0.548
(1.00) 		0.452
(1.00) 		0.0775
(1.00) 		0.251
(1.00) 		0.0914
(1.00) 		0.0378
(0.927) 		0.044
(0.927)
16q loss 5 (3%) 157 0.701
(1.00) 		0.131
(1.00) 		0.588
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
17p loss 62 (38%) 100 0.957
(1.00) 		0.67
(1.00) 		0.0179
(0.704) 		0.42
(1.00) 		0.37
(1.00) 		0.144
(1.00) 		0.076
(1.00) 		0.301
(1.00) 		0.232
(1.00)
17q loss 15 (9%) 147 0.237
(1.00) 		0.599
(1.00) 		0.0758
(1.00) 		0.593
(1.00) 		1
(1.00) 		0.189
(1.00) 		0.386
(1.00) 		0.292
(1.00) 		0.834
(1.00)
18p loss 16 (10%) 146 0.462
(1.00) 		0.511
(1.00) 		1
(1.00) 		0.19
(1.00) 		1
(1.00) 		0.529
(1.00) 		0.298
(1.00) 		0.176
(1.00)
18q loss 6 (4%) 156 0.697
(1.00) 		0.435
(1.00) 		0.277
(1.00) 		0.413
(1.00) 		1
(1.00) 		0.161
(1.00) 		0.148
(1.00)
19q loss 5 (3%) 157 0.659
(1.00) 		0.498
(1.00) 		0.0367
(0.927) 		1
(1.00) 		1
(1.00) 		0.247
(1.00) 		0.0319
(0.906) 		0.189
(1.00)
20q loss 3 (2%) 159 0.832
(1.00) 		0.751
(1.00) 		0.436
(1.00) 		1
(1.00) 		1
(1.00) 		0.216
(1.00) 		1
(1.00)
21q loss 36 (22%) 126 0.201
(1.00) 		0.588
(1.00) 		0.0438
(0.927) 		0.705
(1.00) 		1
(1.00) 		0.39
(1.00) 		0.161
(1.00) 		0.207
(1.00)
22q loss 58 (36%) 104 0.0063
(0.545) 		0.388
(1.00) 		0.088
(1.00) 		0.742
(1.00) 		1
(1.00) 		0.765
(1.00) 		0.149
(1.00) 		0.0136
(0.614) 		0.67
(1.00)
xp loss 48 (30%) 114 0.853
(1.00) 		0.958
(1.00) 		0.821
(1.00) 		0.733
(1.00) 		1
(1.00) 		0.915
(1.00) 		0.143
(1.00) 		0.9
(1.00) 		0.564
(1.00)
xq loss 49 (30%) 113 0.876
(1.00) 		0.926
(1.00) 		0.823
(1.00) 		0.865
(1.00) 		1
(1.00) 		0.781
(1.00) 		0.147
(1.00) 		0.9
(1.00) 		0.614
(1.00)
'1q gain' versus 'RADIATION_THERAPY'

P value = 0.00068 (Fisher's exact test), Q value = 0.11

Table S1.  Gene #2: '1q gain' versus Clinical Feature #5: 'RADIATION_THERAPY'

nPatients NO YES
ALL 155 5
1Q GAIN MUTATED 15 4
1Q GAIN WILD-TYPE 140 1

Figure S1.  Get High-res Image Gene #2: '1q gain' versus Clinical Feature #5: 'RADIATION_THERAPY'

'20q gain' versus 'KARNOFSKY_PERFORMANCE_SCORE'

P value = 0.000306 (Wilcoxon-test), Q value = 0.064

Table S2.  Gene #32: '20q gain' versus Clinical Feature #6: 'KARNOFSKY_PERFORMANCE_SCORE'

nPatients Mean (Std.Dev)
ALL 60 96.8 (6.2)
20Q GAIN MUTATED 4 85.0 (10.0)
20Q GAIN WILD-TYPE 56 97.7 (5.0)

Figure S2.  Get High-res Image Gene #32: '20q gain' versus Clinical Feature #6: 'KARNOFSKY_PERFORMANCE_SCORE'

'12p loss' versus 'Time to Death'

P value = 2.26e-05 (logrank test), Q value = 0.014

Table S3.  Gene #55: '12p loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 162 6 0.1 - 316.7 (24.9)
12P LOSS MUTATED 3 1 2.9 - 17.9 (15.5)
12P LOSS WILD-TYPE 159 5 0.1 - 316.7 (25.2)

Figure S3.  Get High-res Image Gene #55: '12p loss' versus Clinical Feature #1: 'Time to Death'

'16p loss' versus 'Time to Death'

P value = 6.78e-05 (logrank test), Q value = 0.021

Table S4.  Gene #59: '16p loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 162 6 0.1 - 316.7 (24.9)
16P LOSS MUTATED 9 3 0.8 - 117.1 (23.8)
16P LOSS WILD-TYPE 153 3 0.1 - 316.7 (25.2)

Figure S4.  Get High-res Image Gene #59: '16p loss' versus Clinical Feature #1: 'Time to Death'

Methods & Data
Input

  • Copy number data file = broad_values_by_arm.txt from GISTIC pipeline

  • Processed Copy number data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/PCPG-TP/22533878/transformed.cor.cli.txt

  • Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/PCPG-TP/22506925/PCPG-TP.merged_data.txt

  • Number of patients = 162

  • Number of significantly arm-level cnvs = 70

  • Number of selected clinical features = 9

  • Exclude regions 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

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

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] 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)
[3] 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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