Correlation between copy number variations of arm-level result and selected clinical features
Pheochromocytoma and Paraganglioma (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C15Q4VCN
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between copy number variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C15Q4VCN
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 69 arm-level events and 9 clinical features across 162 patients, 2 significant findings detected with Q value < 0.25.

  • 20q gain cnv correlated to 'KARNOFSKY_PERFORMANCE_SCORE'.

  • 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 69 arm-level events and 9 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 		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
20q gain 10 (6%) 152 0.516
(1.00) 		0.333
(1.00) 		0.213
(1.00) 		0.756
(1.00) 		1
(1.00) 		0.000152
(0.0472) 		0.806
(1.00) 		1
(1.00)
16p loss 9 (6%) 153 6.92e-05
(0.043) 		0.124
(1.00) 		0.655
(1.00) 		0.733
(1.00) 		0.0259
(1.00) 		0.318
(1.00) 		0.72
(1.00)
1p gain 7 (4%) 155 0.421
(1.00) 		0.419
(1.00) 		1
(1.00) 		0.048
(1.00) 		0.203
(1.00) 		0.825
(1.00) 		0.728
(1.00) 		1
(1.00)
1q gain 19 (12%) 143 0.502
(1.00) 		0.0891
(1.00) 		0.746
(1.00) 		0.141
(1.00) 		0.0123
(0.908) 		0.876
(1.00) 		0.778
(1.00) 		0.292
(1.00) 		0.855
(1.00)
2p gain 6 (4%) 156 0.612
(1.00) 		0.968
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.672
(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) 		0.209
(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 0.502
(1.00) 		0.225
(1.00) 		0.214
(1.00) 		0.756
(1.00) 		1
(1.00) 		0.852
(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) 		0.76
(1.00) 		1
(1.00) 		1
(1.00)
6p gain 15 (9%) 147 0.483
(1.00) 		0.0416
(1.00) 		0.472
(1.00) 		1
(1.00) 		1
(1.00) 		0.286
(1.00) 		0.538
(1.00) 		1
(1.00)
6q gain 8 (5%) 154 0.604
(1.00) 		0.071
(1.00) 		0.353
(1.00) 		1
(1.00) 		1
(1.00) 		0.0451
(1.00) 		1
(1.00) 		0.459
(1.00)
7p gain 27 (17%) 135 0.324
(1.00) 		0.694
(1.00) 		0.171
(1.00) 		0.53
(1.00) 		0.59
(1.00) 		0.429
(1.00) 		0.483
(1.00) 		0.616
(1.00)
7q gain 22 (14%) 140 0.399
(1.00) 		0.845
(1.00) 		0.769
(1.00) 		0.106
(1.00) 		1
(1.00) 		0.811
(1.00) 		1
(1.00) 		1
(1.00)
8p gain 10 (6%) 152 0.557
(1.00) 		0.211
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.339
(1.00) 		0.503
(1.00) 		0.568
(1.00)
8q gain 13 (8%) 149 0.316
(1.00) 		0.851
(1.00) 		0.47
(1.00) 		0.259
(1.00) 		1
(1.00) 		0.263
(1.00) 		0.499
(1.00) 		0.34
(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) 		0.501
(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) 		0.405
(1.00)
10p gain 12 (7%) 150 0.544
(1.00) 		0.972
(1.00) 		0.129
(1.00) 		1
(1.00) 		1
(1.00) 		0.469
(1.00) 		0.761
(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) 		0.807
(1.00) 		1
(1.00)
11p gain 5 (3%) 157 0.686
(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 0.516
(1.00) 		0.266
(1.00) 		0.214
(1.00) 		1
(1.00) 		1
(1.00) 		0.499
(1.00) 		0.669
(1.00) 		0.76
(1.00)
12q gain 14 (9%) 148 0.467
(1.00) 		0.661
(1.00) 		0.131
(1.00) 		1
(1.00) 		1
(1.00) 		0.286
(1.00) 		0.36
(1.00) 		0.82
(1.00)
13q gain 9 (6%) 153 0.595
(1.00) 		0.829
(1.00) 		1
(1.00) 		0.733
(1.00) 		1
(1.00) 		0.499
(1.00) 		1
(1.00) 		1
(1.00)
14q gain 4 (2%) 158 0.00704
(0.729) 		0.901
(1.00) 		1
(1.00) 		0.332
(1.00) 		1
(1.00) 		1
(1.00) 		0.498
(1.00)
15q gain 14 (9%) 148 0.48
(1.00) 		0.406
(1.00) 		0.131
(1.00) 		0.784
(1.00) 		1
(1.00) 		0.66
(1.00) 		0.359
(1.00) 		0.247
(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 0.0658
(1.00) 		0.0753
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.671
(1.00) 		0.651
(1.00)
17q gain 5 (3%) 157 0.694
(1.00) 		0.591
(1.00) 		0.588
(1.00) 		0.179
(1.00) 		1
(1.00) 		1
(1.00) 		0.582
(1.00)
18p gain 8 (5%) 154 0.563
(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 0.526
(1.00) 		0.611
(1.00) 		0.213
(1.00) 		1
(1.00) 		1
(1.00) 		0.098
(1.00) 		0.807
(1.00) 		1
(1.00)
19p gain 20 (12%) 142 0.708
(1.00) 		0.019
(0.908) 		0.203
(1.00) 		0.638
(1.00) 		0.473
(1.00) 		0.733
(1.00) 		0.489
(1.00) 		1
(1.00)
19q gain 14 (9%) 148 0.468
(1.00) 		0.0235
(1.00) 		0.131
(1.00) 		1
(1.00) 		1
(1.00) 		0.66
(1.00) 		0.358
(1.00) 		0.823
(1.00)
20p gain 12 (7%) 150 0.502
(1.00) 		0.294
(1.00) 		0.693
(1.00) 		1
(1.00) 		1
(1.00) 		0.00157
(0.325) 		0.686
(1.00) 		0.606
(1.00)
21q gain 3 (2%) 159 0.763
(1.00) 		0.0182
(0.908) 		1
(1.00) 		0.593
(1.00) 		1
(1.00) 		1
(1.00) 		0.403
(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) 		0.404
(1.00)
xp gain 6 (4%) 156 0.621
(1.00) 		0.842
(1.00) 		0.591
(1.00) 		0.221
(1.00) 		1
(1.00) 		1
(1.00) 		0.337
(1.00)
xq gain 5 (3%) 157 0.658
(1.00) 		0.958
(1.00) 		0.588
(1.00) 		0.377
(1.00) 		1
(1.00) 		1
(1.00) 		0.582
(1.00)
1p loss 98 (60%) 64 0.197
(1.00) 		0.894
(1.00) 		0.678
(1.00) 		0.748
(1.00) 		0.649
(1.00) 		0.967
(1.00) 		0.849
(1.00) 		0.654
(1.00) 		0.233
(1.00)
1q loss 27 (17%) 135 0.929
(1.00) 		0.927
(1.00) 		0.262
(1.00) 		0.53
(1.00) 		1
(1.00) 		0.56
(1.00) 		0.0628
(1.00) 		0.292
(1.00) 		0.222
(1.00)
2p loss 10 (6%) 152 0.628
(1.00) 		0.636
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.499
(1.00) 		0.505
(1.00) 		0.401
(1.00)
2q loss 13 (8%) 149 0.478
(1.00) 		0.995
(1.00) 		0.0114
(0.908) 		0.259
(1.00) 		1
(1.00) 		0.76
(1.00) 		0.0331
(1.00) 		0.53
(1.00)
3p loss 62 (38%) 100 0.535
(1.00) 		0.307
(1.00) 		0.2
(1.00) 		0.195
(1.00) 		0.37
(1.00) 		0.248
(1.00) 		0.418
(1.00) 		0.358
(1.00) 		0.0689
(1.00)
3q loss 88 (54%) 74 0.313
(1.00) 		0.145
(1.00) 		0.836
(1.00) 		0.875
(1.00) 		1
(1.00) 		0.274
(1.00) 		0.777
(1.00) 		0.535
(1.00) 		0.934
(1.00)
4p loss 11 (7%) 151 0.611
(1.00) 		0.823
(1.00) 		0.691
(1.00) 		0.551
(1.00) 		1
(1.00) 		0.143
(1.00) 		1
(1.00) 		1
(1.00)
4q loss 10 (6%) 152 0.597
(1.00) 		0.989
(1.00) 		0.213
(1.00) 		0.514
(1.00) 		1
(1.00) 		0.143
(1.00) 		0.807
(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) 		0.581
(1.00)
5q loss 7 (4%) 155 0.69
(1.00) 		0.751
(1.00) 		0.605
(1.00) 		0.703
(1.00) 		1
(1.00) 		1
(1.00) 		0.652
(1.00) 		0.399
(1.00)
6q loss 19 (12%) 143 0.61
(1.00) 		0.859
(1.00) 		0.0464
(1.00) 		0.469
(1.00) 		1
(1.00) 		0.527
(1.00) 		0.15
(1.00) 		1
(1.00) 		0.857
(1.00)
7q loss 6 (4%) 156 0.0829
(1.00) 		0.683
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.529
(1.00) 		0.671
(1.00) 		0.0184
(0.908)
8p loss 20 (12%) 142 0.202
(1.00) 		0.249
(1.00) 		0.203
(1.00) 		0.346
(1.00) 		0.492
(1.00) 		0.623
(1.00) 		0.123
(1.00) 		0.507
(1.00)
8q loss 12 (7%) 150 0.315
(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 0.0272
(1.00) 		0.704
(1.00) 		1
(1.00) 		1
(1.00) 		0.0385
(1.00) 		0.00286
(0.443) 		0.424
(1.00) 		1
(1.00)
9q loss 11 (7%) 151 0.557
(1.00) 		0.316
(1.00) 		1
(1.00) 		1
(1.00) 		0.0385
(1.00) 		0.422
(1.00) 		0.759
(1.00)
11p loss 54 (33%) 108 0.548
(1.00) 		0.919
(1.00) 		0.511
(1.00) 		0.316
(1.00) 		0.663
(1.00) 		0.81
(1.00) 		0.567
(1.00) 		0.133
(1.00) 		0.599
(1.00)
11q loss 40 (25%) 122 0.887
(1.00) 		0.712
(1.00) 		0.472
(1.00) 		0.856
(1.00) 		0.332
(1.00) 		0.58
(1.00) 		0.541
(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) 		0.744
(1.00) 		1
(1.00) 		0.314
(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) 		0.539
(1.00) 		0.553
(1.00) 		0.672
(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) 		0.0377
(1.00) 		0.0443
(1.00)
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 61 (38%) 101 0.972
(1.00) 		0.761
(1.00) 		0.0187
(0.908) 		0.332
(1.00) 		0.364
(1.00) 		0.193
(1.00) 		0.0901
(1.00) 		0.44
(1.00) 		0.0805
(1.00)
17q loss 19 (12%) 143 0.0972
(1.00) 		0.585
(1.00) 		0.201
(1.00) 		0.328
(1.00) 		0.0976
(1.00) 		0.303
(1.00) 		0.317
(1.00) 		0.756
(1.00)
18p loss 16 (10%) 146 0.461
(1.00) 		0.511
(1.00) 		1
(1.00) 		0.19
(1.00) 		1
(1.00) 		0.499
(1.00) 		0.298
(1.00) 		0.173
(1.00)
18q loss 6 (4%) 156 0.696
(1.00) 		0.435
(1.00) 		0.277
(1.00) 		0.413
(1.00) 		1
(1.00) 		0.159
(1.00) 		0.147
(1.00)
19q loss 6 (4%) 156 0.0785
(1.00) 		0.723
(1.00) 		0.0648
(1.00) 		1
(1.00) 		1
(1.00) 		0.263
(1.00) 		0.0592
(1.00) 		0.228
(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) 		0.217
(1.00) 		1
(1.00)
21q loss 36 (22%) 126 0.201
(1.00) 		0.588
(1.00) 		0.0438
(1.00) 		0.705
(1.00) 		1
(1.00) 		0.295
(1.00) 		0.162
(1.00) 		0.208
(1.00)
22q loss 58 (36%) 104 0.00641
(0.729) 		0.388
(1.00) 		0.088
(1.00) 		0.742
(1.00) 		1
(1.00) 		0.617
(1.00) 		0.148
(1.00) 		0.0136
(0.908) 		0.67
(1.00)
xp loss 48 (30%) 114 0.846
(1.00) 		0.958
(1.00) 		0.821
(1.00) 		0.733
(1.00) 		1
(1.00) 		0.5
(1.00) 		0.144
(1.00) 		0.9
(1.00) 		0.563
(1.00)
xq loss 49 (30%) 113 0.869
(1.00) 		0.926
(1.00) 		0.823
(1.00) 		0.865
(1.00) 		1
(1.00) 		0.408
(1.00) 		0.147
(1.00) 		0.9
(1.00) 		0.614
(1.00)
'20q gain' versus 'KARNOFSKY_PERFORMANCE_SCORE'

P value = 0.000152 (Wilcoxon-test), Q value = 0.047

Table S1.  Gene #32: '20q gain' versus Clinical Feature #6: 'KARNOFSKY_PERFORMANCE_SCORE'

nPatients Mean (Std.Dev)
ALL 59 97.1 (5.9)
20Q GAIN MUTATED 4 85.0 (10.0)
20Q GAIN WILD-TYPE 55 98.0 (4.5)

Figure S1.  Get High-res Image Gene #32: '20q gain' versus Clinical Feature #6: 'KARNOFSKY_PERFORMANCE_SCORE'

'16p loss' versus 'Time to Death'

P value = 6.92e-05 (logrank test), Q value = 0.043

Table S2.  Gene #58: '16p loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 161 6 0.1 - 316.7 (25.1)
16P LOSS MUTATED 9 3 0.8 - 117.1 (23.8)
16P LOSS WILD-TYPE 152 3 0.1 - 316.7 (25.2)

Figure S2.  Get High-res Image Gene #58: '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/19781941/transformed.cor.cli.txt

  • Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/PCPG-TP/19775435/PCPG-TP.merged_data.txt

  • Number of patients = 162

  • Number of significantly arm-level cnvs = 69

  • 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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