Correlation between copy number variations of arm-level result and selected clinical features
Adrenocortical Carcinoma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
Maintainer Information
Citation Information
doi:10.7908/C18914K9
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 variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C18914K9
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 75 arm-level events and 7 clinical features across 80 patients, one significant finding detected with Q value < 0.25.

  • 4q 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 75 arm-level events and 7 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, one significant finding detected.

Clinical
Features 		Time
to
Death 		AGE NEOPLASM
DISEASESTAGE 		PATHOLOGY
T
STAGE 		PATHOLOGY
N
STAGE 		GENDER ETHNICITY
nCNV (%) nWild-Type logrank test Wilcoxon-test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
4q loss 10 (12%) 70 6.33e-05
(0.0332) 		0.631
(1.00) 		0.0923
(1.00) 		0.0223
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
1q gain 6 (8%) 74 0.0526
(1.00) 		0.584
(1.00) 		0.747
(1.00) 		0.338
(1.00) 		1
(1.00) 		0.086
(1.00) 		0.41
(1.00)
2p gain 11 (14%) 69 0.00663
(1.00) 		1
(1.00) 		0.469
(1.00) 		0.211
(1.00) 		0.341
(1.00) 		0.312
(1.00) 		0.568
(1.00)
2q gain 9 (11%) 71 0.0684
(1.00) 		0.675
(1.00) 		0.0338
(1.00) 		0.136
(1.00) 		1
(1.00) 		0.15
(1.00) 		0.602
(1.00)
3p gain 10 (12%) 70 0.344
(1.00) 		0.749
(1.00) 		0.49
(1.00) 		0.911
(1.00) 		1
(1.00) 		0.734
(1.00) 		1
(1.00)
3q gain 12 (15%) 68 0.502
(1.00) 		0.666
(1.00) 		0.325
(1.00) 		0.927
(1.00) 		0.65
(1.00) 		1
(1.00) 		1
(1.00)
4p gain 32 (40%) 48 0.239
(1.00) 		0.817
(1.00) 		0.832
(1.00) 		0.85
(1.00) 		1
(1.00) 		0.812
(1.00) 		0.186
(1.00)
4q gain 29 (36%) 51 0.183
(1.00) 		0.924
(1.00) 		0.891
(1.00) 		0.894
(1.00) 		1
(1.00) 		0.808
(1.00) 		0.346
(1.00)
5p gain 51 (64%) 29 0.363
(1.00) 		0.932
(1.00) 		0.544
(1.00) 		0.948
(1.00) 		0.734
(1.00) 		0.808
(1.00) 		0.21
(1.00)
5q gain 49 (61%) 31 0.571
(1.00) 		0.628
(1.00) 		0.592
(1.00) 		0.728
(1.00) 		1
(1.00) 		0.342
(1.00) 		0.21
(1.00)
6p gain 16 (20%) 64 0.526
(1.00) 		0.0146
(1.00) 		0.494
(1.00) 		0.302
(1.00) 		0.676
(1.00) 		0.779
(1.00) 		0.0596
(1.00)
6q gain 14 (18%) 66 0.932
(1.00) 		0.133
(1.00) 		0.229
(1.00) 		0.357
(1.00) 		0.197
(1.00) 		0.226
(1.00) 		0.602
(1.00)
7p gain 42 (52%) 38 0.643
(1.00) 		0.916
(1.00) 		0.22
(1.00) 		0.343
(1.00) 		0.332
(1.00) 		0.816
(1.00) 		0.244
(1.00)
7q gain 42 (52%) 38 0.559
(1.00) 		0.689
(1.00) 		0.158
(1.00) 		0.374
(1.00) 		0.332
(1.00) 		0.816
(1.00) 		0.101
(1.00)
8p gain 30 (38%) 50 0.635
(1.00) 		0.415
(1.00) 		0.34
(1.00) 		0.577
(1.00) 		0.304
(1.00) 		1
(1.00) 		0.433
(1.00)
8q gain 34 (42%) 46 0.694
(1.00) 		0.988
(1.00) 		0.449
(1.00) 		0.625
(1.00) 		0.502
(1.00) 		1
(1.00) 		0.685
(1.00)
9p gain 16 (20%) 64 0.0164
(1.00) 		0.705
(1.00) 		0.0278
(1.00) 		0.273
(1.00) 		0.00421
(1.00) 		0.397
(1.00) 		0.312
(1.00)
9q gain 24 (30%) 56 0.000866
(0.451) 		0.741
(1.00) 		0.0123
(1.00) 		0.0957
(1.00) 		0.00838
(1.00) 		0.307
(1.00) 		0.226
(1.00)
10p gain 22 (28%) 58 0.0224
(1.00) 		0.397
(1.00) 		0.0148
(1.00) 		0.0281
(1.00) 		1
(1.00) 		1
(1.00) 		0.433
(1.00)
10q gain 23 (29%) 57 0.00385
(1.00) 		0.398
(1.00) 		0.00485
(1.00) 		0.0103
(1.00) 		1
(1.00) 		1
(1.00) 		0.433
(1.00)
11p gain 3 (4%) 77 0.732
(1.00) 		0.176
(1.00) 		0.0323
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
11q gain 4 (5%) 76 0.00194
(1.00) 		0.842
(1.00) 		0.0453
(1.00) 		0.0399
(1.00) 		1
(1.00) 		1
(1.00) 		0.553
(1.00)
12p gain 56 (70%) 24 0.924
(1.00) 		0.2
(1.00) 		0.926
(1.00) 		0.869
(1.00) 		1
(1.00) 		0.611
(1.00) 		0.0734
(1.00)
12q gain 57 (71%) 23 0.709
(1.00) 		0.266
(1.00) 		0.745
(1.00) 		0.835
(1.00) 		0.719
(1.00) 		0.796
(1.00) 		0.0815
(1.00)
13q gain 5 (6%) 75 0.895
(1.00) 		0.835
(1.00) 		0.434
(1.00) 		0.609
(1.00) 		0.511
(1.00) 		0.653
(1.00) 		0.553
(1.00)
14q gain 18 (22%) 62 0.514
(1.00) 		0.284
(1.00) 		0.291
(1.00) 		0.383
(1.00) 		0.231
(1.00) 		1
(1.00) 		0.346
(1.00)
15q gain 10 (12%) 70 0.699
(1.00) 		0.805
(1.00) 		0.781
(1.00) 		0.633
(1.00) 		1
(1.00) 		0.734
(1.00) 		1
(1.00)
16p gain 43 (54%) 37 0.225
(1.00) 		0.469
(1.00) 		0.721
(1.00) 		0.483
(1.00) 		1
(1.00) 		0.481
(1.00) 		0.443
(1.00)
16q gain 43 (54%) 37 0.304
(1.00) 		0.881
(1.00) 		0.856
(1.00) 		0.457
(1.00) 		1
(1.00) 		0.815
(1.00) 		0.443
(1.00)
17p gain 4 (5%) 76 0.542
(1.00) 		0.459
(1.00) 		0.716
(1.00) 		0.167
(1.00) 		1
(1.00) 		0.609
(1.00) 		0.41
(1.00)
17q gain 5 (6%) 75 0.955
(1.00) 		0.788
(1.00) 		0.908
(1.00) 		0.402
(1.00) 		1
(1.00) 		1
(1.00) 		0.41
(1.00)
19p gain 49 (61%) 31 0.496
(1.00) 		0.0579
(1.00) 		0.166
(1.00) 		0.266
(1.00) 		0.734
(1.00) 		1
(1.00) 		0.108
(1.00)
19q gain 45 (56%) 35 0.584
(1.00) 		0.0241
(1.00) 		0.423
(1.00) 		0.576
(1.00) 		0.174
(1.00) 		0.64
(1.00) 		0.108
(1.00)
20p gain 41 (51%) 39 0.197
(1.00) 		0.5
(1.00) 		0.367
(1.00) 		0.716
(1.00) 		1
(1.00) 		0.488
(1.00) 		1
(1.00)
20q gain 44 (55%) 36 0.267
(1.00) 		0.977
(1.00) 		0.482
(1.00) 		0.827
(1.00) 		0.498
(1.00) 		0.247
(1.00) 		0.7
(1.00)
21q gain 26 (32%) 54 0.919
(1.00) 		0.0705
(1.00) 		1
(1.00) 		0.913
(1.00) 		0.0692
(1.00) 		0.803
(1.00) 		0.402
(1.00)
xq gain 35 (44%) 45 0.5
(1.00) 		0.756
(1.00) 		0.825
(1.00) 		1
(1.00) 		0.332
(1.00) 		1
(1.00) 		0.244
(1.00)
1p loss 27 (34%) 53 0.38
(1.00) 		0.963
(1.00) 		0.628
(1.00) 		0.543
(1.00) 		1
(1.00) 		0.808
(1.00) 		1
(1.00)
1q loss 18 (22%) 62 0.861
(1.00) 		0.174
(1.00) 		0.859
(1.00) 		0.885
(1.00) 		0.683
(1.00) 		0.404
(1.00) 		1
(1.00)
2p loss 17 (21%) 63 0.0455
(1.00) 		0.444
(1.00) 		0.925
(1.00) 		0.648
(1.00) 		1
(1.00) 		0.576
(1.00) 		1
(1.00)
2q loss 15 (19%) 65 0.0825
(1.00) 		0.707
(1.00) 		0.505
(1.00) 		0.693
(1.00) 		0.679
(1.00) 		0.766
(1.00) 		1
(1.00)
3p loss 18 (22%) 62 0.0617
(1.00) 		0.433
(1.00) 		0.179
(1.00) 		0.484
(1.00) 		1
(1.00) 		0.164
(1.00) 		0.553
(1.00)
3q loss 18 (22%) 62 0.143
(1.00) 		0.695
(1.00) 		0.289
(1.00) 		0.711
(1.00) 		1
(1.00) 		0.404
(1.00) 		0.218
(1.00)
4p loss 9 (11%) 71 0.000545
(0.285) 		0.389
(1.00) 		0.0667
(1.00) 		0.0106
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
5p loss 7 (9%) 73 0.386
(1.00) 		0.759
(1.00) 		0.565
(1.00) 		0.194
(1.00) 		1
(1.00) 		0.691
(1.00) 		0.553
(1.00)
5q loss 6 (8%) 74 0.972
(1.00) 		0.371
(1.00) 		0.248
(1.00) 		0.363
(1.00) 		0.579
(1.00) 		0.176
(1.00) 		1
(1.00)
6p loss 17 (21%) 63 0.174
(1.00) 		0.488
(1.00) 		0.147
(1.00) 		0.213
(1.00) 		0.683
(1.00) 		1
(1.00) 		0.553
(1.00)
6q loss 20 (25%) 60 0.119
(1.00) 		0.353
(1.00) 		0.0244
(1.00) 		0.0393
(1.00) 		0.714
(1.00) 		0.787
(1.00) 		1
(1.00)
7p loss 4 (5%) 76 0.328
(1.00) 		0.86
(1.00) 		0.502
(1.00) 		0.563
(1.00) 		1
(1.00) 		0.0129
(1.00) 		1
(1.00)
7q loss 5 (6%) 75 0.308
(1.00) 		0.72
(1.00) 		0.0212
(1.00) 		0.0339
(1.00) 		1
(1.00) 		0.337
(1.00) 		1
(1.00)
8p loss 13 (16%) 67 0.602
(1.00) 		0.835
(1.00) 		0.743
(1.00) 		1
(1.00) 		0.183
(1.00) 		0.761
(1.00) 		1
(1.00)
8q loss 10 (12%) 70 0.979
(1.00) 		0.777
(1.00) 		0.843
(1.00) 		1
(1.00) 		0.0881
(1.00) 		1
(1.00) 		1
(1.00)
9p loss 19 (24%) 61 0.25
(1.00) 		0.623
(1.00) 		0.885
(1.00) 		0.621
(1.00) 		0.437
(1.00) 		0.583
(1.00) 		1
(1.00)
9q loss 10 (12%) 70 0.776
(1.00) 		0.595
(1.00) 		0.195
(1.00) 		0.327
(1.00) 		0.596
(1.00) 		0.734
(1.00) 		0.553
(1.00)
10p loss 11 (14%) 69 0.356
(1.00) 		0.675
(1.00) 		0.183
(1.00) 		1
(1.00) 		0.149
(1.00) 		1
(1.00) 		0.41
(1.00)
10q loss 9 (11%) 71 0.401
(1.00) 		0.594
(1.00) 		0.318
(1.00) 		0.631
(1.00) 		0.331
(1.00) 		1
(1.00) 		1
(1.00)
11p loss 23 (29%) 57 0.716
(1.00) 		0.844
(1.00) 		0.141
(1.00) 		0.588
(1.00) 		1
(1.00) 		0.438
(1.00) 		1
(1.00)
11q loss 22 (28%) 58 0.264
(1.00) 		0.682
(1.00) 		0.0224
(1.00) 		0.134
(1.00) 		1
(1.00) 		0.295
(1.00) 		0.553
(1.00)
12p loss 5 (6%) 75 0.233
(1.00) 		0.266
(1.00) 		0.715
(1.00) 		0.388
(1.00) 		1
(1.00) 		0.337
(1.00) 		1
(1.00)
12q loss 4 (5%) 76 0.0823
(1.00) 		0.508
(1.00) 		0.716
(1.00) 		0.387
(1.00) 		1
(1.00) 		0.609
(1.00) 		1
(1.00)
13q loss 33 (41%) 47 0.139
(1.00) 		0.973
(1.00) 		0.605
(1.00) 		0.86
(1.00) 		0.731
(1.00) 		0.341
(1.00) 		1
(1.00)
14q loss 17 (21%) 63 0.338
(1.00) 		0.828
(1.00) 		0.431
(1.00) 		0.421
(1.00) 		0.443
(1.00) 		0.576
(1.00) 		0.312
(1.00)
15q loss 20 (25%) 60 0.502
(1.00) 		0.56
(1.00) 		0.827
(1.00) 		0.84
(1.00) 		1
(1.00) 		0.787
(1.00) 		0.648
(1.00)
16p loss 6 (8%) 74 0.000586
(0.306) 		0.427
(1.00) 		0.247
(1.00) 		0.0648
(1.00) 		0.579
(1.00) 		1
(1.00) 		0.553
(1.00)
16q loss 5 (6%) 75 0.0227
(1.00) 		0.2
(1.00) 		0.433
(1.00) 		0.187
(1.00) 		0.511
(1.00) 		1
(1.00) 		0.553
(1.00)
17p loss 29 (36%) 51 0.00141
(0.733) 		0.389
(1.00) 		0.0828
(1.00) 		0.11
(1.00) 		0.734
(1.00) 		0.0876
(1.00) 		0.39
(1.00)
17q loss 24 (30%) 56 0.00832
(1.00) 		0.946
(1.00) 		0.0656
(1.00) 		0.11
(1.00) 		1
(1.00) 		0.00949
(1.00) 		0.39
(1.00)
18p loss 36 (45%) 44 0.745
(1.00) 		0.973
(1.00) 		0.14
(1.00) 		0.334
(1.00) 		1
(1.00) 		0.347
(1.00) 		1
(1.00)
18q loss 34 (42%) 46 0.851
(1.00) 		0.819
(1.00) 		0.124
(1.00) 		0.23
(1.00) 		1
(1.00) 		0.0615
(1.00) 		1
(1.00)
19p loss 3 (4%) 77 0.00472
(1.00) 		0.78
(1.00) 		0.505
(1.00) 		0.453
(1.00) 		1
(1.00) 		0.279
(1.00) 		1
(1.00)
19q loss 3 (4%) 77 0.0389
(1.00) 		0.234
(1.00) 		0.861
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
20p loss 7 (9%) 73 0.281
(1.00) 		0.409
(1.00) 		0.547
(1.00) 		0.926
(1.00) 		0.579
(1.00) 		0.412
(1.00) 		0.41
(1.00)
21q loss 15 (19%) 65 0.00868
(1.00) 		0.434
(1.00) 		0.426
(1.00) 		0.294
(1.00) 		0.676
(1.00) 		0.557
(1.00) 		1
(1.00)
22q loss 45 (56%) 35 0.00652
(1.00) 		0.467
(1.00) 		0.275
(1.00) 		0.0967
(1.00) 		0.742
(1.00) 		0.159
(1.00) 		0.121
(1.00)
xq loss 15 (19%) 65 0.806
(1.00) 		0.0458
(1.00) 		0.507
(1.00) 		0.283
(1.00) 		0.377
(1.00) 		0.766
(1.00) 		0.315
(1.00)
'4q loss' versus 'Time to Death'

P value = 6.33e-05 (logrank test), Q value = 0.033

Table S1.  Gene #44: '4q loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 79 27 4.1 - 153.6 (31.2)
4Q LOSS MUTATED 10 7 4.1 - 46.5 (18.1)
4Q LOSS WILD-TYPE 69 20 4.9 - 153.6 (36.3)

Figure S1.  Get High-res Image Gene #44: '4q loss' versus Clinical Feature #1: 'Time to Death'

Methods & Data
Input

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

  • Clinical data file = ACC-TP.merged_data.txt

  • Number of patients = 80

  • Number of significantly arm-level cnvs = 75

  • Number of selected clinical features = 7

  • 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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