Correlation between copy number variation genes (focal events) and selected clinical features
Testicular Germ Cell Tumors (Primary solid tumor)
21 August 2015  |  analyses__2015_08_21
Maintainer Information
Citation Information
doi:10.7908/C1765DNP
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 variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1765DNP
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and selected clinical features.

Summary

Testing the association between copy number variation 47 focal events and 10 clinical features across 134 patients, 5 significant findings detected with Q value < 0.25.

  • del_10p15.3 cnv correlated to 'YEARS_TO_BIRTH'.

  • del_10q23.1 cnv correlated to 'YEARS_TO_BIRTH'.

  • del_19q13.41 cnv correlated to 'YEARS_TO_BIRTH',  'PATHOLOGIC_STAGE', and 'RADIATION_THERAPY'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 47 focal events and 10 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 5 significant findings detected.

Clinical
Features 		Time
to
Death 		YEARS
TO
BIRTH 		PATHOLOGIC
STAGE 		PATHOLOGY
T
STAGE 		PATHOLOGY
N
STAGE 		PATHOLOGY
M
STAGE 		RADIATION
THERAPY 		KARNOFSKY
PERFORMANCE
SCORE 		RACE 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 Wilcoxon-test Fisher's exact test Fisher's exact test
del 19q13 41 47 (35%) 87 0.152
(0.89) 		0.000526
(0.0823) 		0.0004
(0.0823) 		0.368
(0.981) 		0.128
(0.89) 		0.619
(1.00) 		0.000133
(0.0626) 		0.558
(1.00) 		0.764
(1.00) 		1
(1.00)
del 10p15 3 72 (54%) 62 0.526
(1.00) 		0.00228
(0.215) 		0.124
(0.89) 		0.495
(1.00) 		0.203
(0.962) 		0.125
(0.89) 		0.045
(0.784) 		0.0506
(0.784) 		0.0511
(0.784) 		0.766
(1.00)
del 10q23 1 62 (46%) 72 0.287
(0.981) 		0.00195
(0.215) 		0.0433
(0.784) 		0.297
(0.981) 		0.0303
(0.751) 		0.328
(0.981) 		0.0244
(0.693) 		0.105
(0.89) 		0.472
(1.00) 		0.139
(0.89)
amp 1q21 2 63 (47%) 71 0.91
(1.00) 		0.163
(0.895) 		0.488
(1.00) 		0.955
(1.00) 		0.532
(1.00) 		0.619
(1.00) 		0.333
(0.981) 		0.926
(1.00) 		0.267
(0.981) 		0.0678
(0.826)
amp 2p24 1 53 (40%) 81 0.69
(1.00) 		0.888
(1.00) 		0.914
(1.00) 		0.262
(0.981) 		0.351
(0.981) 		0.64
(1.00) 		0.45
(1.00) 		0.139
(0.89) 		0.673
(1.00) 		0.364
(0.981)
amp 3q27 3 41 (31%) 93 0.864
(1.00) 		0.772
(1.00) 		0.715
(1.00) 		0.11
(0.89) 		1
(1.00) 		0.583
(1.00) 		0.423
(1.00) 		0.547
(1.00) 		0.482
(1.00) 		0.344
(0.981)
amp 4q12 19 (14%) 115 0.382
(0.982) 		0.274
(0.981) 		0.534
(1.00) 		0.917
(1.00) 		1
(1.00) 		1
(1.00) 		0.143
(0.89) 		0.881
(1.00) 		1
(1.00) 		1
(1.00)
amp 7p22 1 116 (87%) 18 0.619
(1.00) 		0.581
(1.00) 		0.696
(1.00) 		0.832
(1.00) 		0.668
(1.00) 		0.421
(1.00) 		0.304
(0.981) 		0.917
(1.00) 		0.391
(0.993) 		0.164
(0.895)
amp 7q11 22 110 (82%) 24 0.753
(1.00) 		0.665
(1.00) 		0.309
(0.981) 		0.263
(0.981) 		1
(1.00) 		0.545
(1.00) 		0.754
(1.00) 		0.699
(1.00) 		0.816
(1.00) 		0.123
(0.89)
amp 8q11 23 114 (85%) 20 0.349
(0.981) 		0.923
(1.00) 		0.45
(1.00) 		0.703
(1.00) 		0.668
(1.00) 		0.0869
(0.888) 		0.304
(0.981) 		0.362
(0.981) 		0.3
(0.981) 		0.655
(1.00)
amp 8q23 3 101 (75%) 33 0.252
(0.981) 		0.573
(1.00) 		0.328
(0.981) 		0.285
(0.981) 		0.713
(1.00) 		0.221
(0.981) 		0.154
(0.89) 		0.212
(0.978) 		0.844
(1.00) 		0.467
(1.00)
amp 12p13 33 129 (96%) 5 0.74
(1.00) 		0.577
(1.00) 		0.412
(1.00) 		0.721
(1.00) 		1
(1.00) 		0.157
(0.89) 		0.631
(1.00) 		1
(1.00) 		1
(1.00)
amp 12p12 1 131 (98%) 3 0.787
(1.00) 		0.552
(1.00) 		0.309
(0.981) 		1
(1.00) 		1
(1.00) 		0.382
(0.982) 		1
(1.00) 		1
(1.00)
amp 12p11 21 128 (96%) 6 0.74
(1.00) 		0.651
(1.00) 		0.902
(1.00) 		0.761
(1.00) 		1
(1.00) 		0.555
(1.00) 		0.631
(1.00) 		1
(1.00) 		0.407
(1.00)
amp 12q15 90 (67%) 44 0.545
(1.00) 		0.0233
(0.693) 		0.574
(1.00) 		0.657
(1.00) 		0.481
(1.00) 		1
(1.00) 		0.184
(0.926) 		0.554
(1.00) 		0.569
(1.00) 		0.517
(1.00)
amp 16q21 19 (14%) 115 0.368
(0.981) 		0.371
(0.981) 		0.278
(0.981) 		0.3
(0.981) 		1
(1.00) 		0.465
(1.00) 		0.737
(1.00) 		0.911
(1.00) 		1
(1.00) 		0.062
(0.809)
amp 20q11 21 41 (31%) 93 0.551
(1.00) 		0.173
(0.913) 		0.0447
(0.784) 		0.0115
(0.492) 		0.481
(1.00) 		0.307
(0.981) 		0.0572
(0.793) 		0.296
(0.981) 		0.484
(1.00) 		1
(1.00)
amp 22q11 21 54 (40%) 80 0.865
(1.00) 		0.101
(0.89) 		0.066
(0.826) 		0.909
(1.00) 		0.152
(0.89) 		0.152
(0.89) 		0.0398
(0.784) 		0.118
(0.89) 		0.781
(1.00) 		0.539
(1.00)
del 1p36 31 29 (22%) 105 0.0494
(0.784) 		0.781
(1.00) 		0.141
(0.89) 		0.87
(1.00) 		1
(1.00) 		1
(1.00) 		0.763
(1.00) 		0.582
(1.00) 		0.692
(1.00) 		0.0564
(0.793)
del 1p31 1 26 (19%) 108 0.0265
(0.693) 		0.811
(1.00) 		0.672
(1.00) 		0.61
(1.00) 		0.712
(1.00) 		0.526
(1.00) 		1
(1.00) 		0.111
(0.89) 		0.423
(1.00) 		1
(1.00)
del 1q42 12 9 (7%) 125 0.059
(0.793) 		0.522
(1.00) 		0.363
(0.981) 		0.451
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.138
(0.89) 		0.0799
(0.874) 		0.522
(1.00)
del 2q37 3 13 (10%) 121 0.148
(0.89) 		0.609
(1.00) 		0.738
(1.00) 		0.43
(1.00) 		0.643
(1.00) 		1
(1.00) 		1
(1.00) 		0.127
(0.89) 		0.0164
(0.643) 		0.0945
(0.89)
del 3p26 2 40 (30%) 94 0.662
(1.00) 		0.344
(0.981) 		0.378
(0.982) 		0.0517
(0.784) 		0.509
(1.00) 		0.322
(0.981) 		0.585
(1.00) 		0.983
(1.00) 		0.295
(0.981) 		0.752
(1.00)
del 4q22 2 100 (75%) 34 0.298
(0.981) 		0.119
(0.89) 		0.26
(0.981) 		0.0697
(0.826) 		0.026
(0.693) 		1
(1.00) 		0.572
(1.00) 		0.411
(1.00) 		0.355
(0.981) 		0.732
(1.00)
del 5p15 2 91 (68%) 43 0.981
(1.00) 		0.694
(1.00) 		0.333
(0.981) 		0.117
(0.89) 		1
(1.00) 		0.592
(1.00) 		0.606
(1.00) 		0.323
(0.981) 		0.567
(1.00) 		0.517
(1.00)
del 5p14 3 93 (69%) 41 0.966
(1.00) 		0.841
(1.00) 		0.394
(0.995) 		0.0376
(0.784) 		1
(1.00) 		0.583
(1.00) 		0.423
(1.00) 		0.555
(1.00) 		0.649
(1.00) 		0.752
(1.00)
del 5q12 1 95 (71%) 39 0.911
(1.00) 		0.571
(1.00) 		0.114
(0.89) 		0.00631
(0.371) 		0.738
(1.00) 		0.58
(1.00) 		0.0584
(0.793) 		0.236
(0.981) 		0.645
(1.00) 		0.745
(1.00)
del 6p22 3 19 (14%) 115 0.905
(1.00) 		0.326
(0.981) 		0.669
(1.00) 		0.621
(1.00) 		0.668
(1.00) 		0.465
(1.00) 		0.0738
(0.826) 		0.922
(1.00) 		0.781
(1.00) 		0.671
(1.00)
del 6q26 22 (16%) 112 0.332
(0.981) 		0.0732
(0.826) 		0.185
(0.926) 		0.662
(1.00) 		1
(1.00) 		0.131
(0.89) 		0.526
(1.00) 		0.9
(1.00) 		1
(1.00) 		0.688
(1.00)
del 7q11 22 3 (2%) 131 0.773
(1.00) 		0.94
(1.00) 		0.8
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.558
(1.00) 		1
(1.00) 		0.267
(0.981)
del 7q36 1 14 (10%) 120 0.543
(1.00) 		0.407
(1.00) 		0.149
(0.89) 		0.889
(1.00) 		0.302
(0.981) 		1
(1.00) 		1
(1.00) 		0.311
(0.981) 		1
(1.00) 		0.0046
(0.309)
del 9p24 3 63 (47%) 71 0.95
(1.00) 		0.592
(1.00) 		0.241
(0.981) 		0.955
(1.00) 		0.54
(1.00) 		0.348
(0.981) 		0.325
(0.981) 		0.926
(1.00) 		0.693
(1.00) 		1
(1.00)
del 9p23 59 (44%) 75 0.864
(1.00) 		0.686
(1.00) 		0.331
(0.981) 		0.831
(1.00) 		1
(1.00) 		0.322
(0.981) 		0.212
(0.978) 		0.945
(1.00) 		0.595
(1.00) 		0.766
(1.00)
del 9q33 3 52 (39%) 82 0.171
(0.912) 		0.551
(1.00) 		0.439
(1.00) 		0.676
(1.00) 		0.755
(1.00) 		0.64
(1.00) 		1
(1.00) 		0.342
(0.981) 		0.449
(1.00) 		0.364
(0.981)
del 9q34 2 52 (39%) 82 0.249
(0.981) 		0.377
(0.982) 		0.371
(0.981) 		0.676
(1.00) 		0.755
(1.00) 		0.64
(1.00) 		1
(1.00) 		0.443
(1.00) 		0.451
(1.00) 		0.124
(0.89)
del 10q26 3 66 (49%) 68 0.315
(0.981) 		0.0043
(0.309) 		0.0109
(0.492) 		0.37
(0.981) 		0.0262
(0.693) 		0.364
(0.981) 		0.135
(0.89) 		0.0487
(0.784) 		0.785
(1.00) 		0.363
(0.981)
del 11p15 5 85 (63%) 49 0.877
(1.00) 		0.248
(0.981) 		0.95
(1.00) 		0.709
(1.00) 		0.184
(0.926) 		1
(1.00) 		0.196
(0.955) 		0.425
(1.00) 		0.765
(1.00) 		0.75
(1.00)
del 11p12 90 (67%) 44 0.615
(1.00) 		0.211
(0.978) 		0.994
(1.00) 		0.403
(1.00) 		0.0838
(0.875) 		1
(1.00) 		0.0328
(0.77) 		0.554
(1.00) 		0.66
(1.00) 		0.753
(1.00)
del 11q12 3 104 (78%) 30 0.957
(1.00) 		0.371
(0.981) 		0.997
(1.00) 		0.273
(0.981) 		0.159
(0.89) 		1
(1.00) 		0.0732
(0.826) 		0.543
(1.00) 		0.143
(0.89) 		0.708
(1.00)
del 11q24 2 110 (82%) 24 0.491
(1.00) 		0.587
(1.00) 		0.742
(1.00) 		0.457
(1.00) 		0.1
(0.89) 		1
(1.00) 		0.197
(0.955) 		0.227
(0.981) 		0.00834
(0.436) 		0.381
(0.982)
del 13q34 102 (76%) 32 0.301
(0.981) 		0.181
(0.926) 		0.621
(1.00) 		0.166
(0.899) 		0.159
(0.89) 		1
(1.00) 		0.155
(0.89) 		0.625
(1.00) 		0.33
(0.981) 		0.73
(1.00)
del 16q23 1 61 (46%) 73 0.114
(0.89) 		0.663
(1.00) 		0.535
(1.00) 		0.291
(0.981) 		1
(1.00) 		0.123
(0.89) 		0.133
(0.89) 		0.784
(1.00) 		0.687
(1.00) 		1
(1.00)
del 18p11 32 106 (79%) 28 0.385
(0.985) 		0.257
(0.981) 		0.662
(1.00) 		0.231
(0.981) 		0.426
(1.00) 		1
(1.00) 		1
(1.00) 		0.29
(0.981) 		0.672
(1.00) 		1
(1.00)
del 18q22 2 113 (84%) 21 0.444
(1.00) 		0.258
(0.981) 		0.455
(1.00) 		0.0829
(0.875) 		0.671
(1.00) 		0.506
(1.00) 		1
(1.00) 		0.526
(1.00) 		0.785
(1.00) 		1
(1.00)
del 20p12 1 27 (20%) 107 0.29
(0.981) 		0.896
(1.00) 		0.351
(0.981) 		0.576
(1.00) 		0.113
(0.89) 		0.194
(0.955) 		0.762
(1.00) 		0.558
(1.00) 		0.574
(1.00) 		0.716
(1.00)
del xp21 1 23 (17%) 111 0.325
(0.981) 		0.763
(1.00) 		0.318
(0.981) 		0.201
(0.962) 		0.185
(0.926) 		1
(1.00) 		0.523
(1.00) 		0.272
(0.981) 		0.0485
(0.784) 		0.411
(1.00)
del xq27 3 25 (19%) 109 0.295
(0.981) 		0.293
(0.981) 		0.0244
(0.693) 		0.401
(1.00) 		0.426
(1.00) 		0.564
(1.00) 		0.529
(1.00) 		0.894
(1.00) 		0.824
(1.00) 		0.235
(0.981)
'del_10p15.3' versus 'YEARS_TO_BIRTH'

P value = 0.00228 (Wilcoxon-test), Q value = 0.21

Table S1.  Gene #33: 'del_10p15.3' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 134 32.0 (9.3)
DEL PEAK 18(10P15.3) MUTATED 72 29.8 (8.6)
DEL PEAK 18(10P15.3) WILD-TYPE 62 34.5 (9.5)

Figure S1.  Get High-res Image Gene #33: 'del_10p15.3' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'del_10q23.1' versus 'YEARS_TO_BIRTH'

P value = 0.00195 (Wilcoxon-test), Q value = 0.21

Table S2.  Gene #34: 'del_10q23.1' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 134 32.0 (9.3)
DEL PEAK 19(10Q23.1) MUTATED 62 29.6 (8.9)
DEL PEAK 19(10Q23.1) WILD-TYPE 72 34.0 (9.2)

Figure S2.  Get High-res Image Gene #34: 'del_10q23.1' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'del_19q13.41' versus 'YEARS_TO_BIRTH'

P value = 0.000526 (Wilcoxon-test), Q value = 0.082

Table S3.  Gene #44: 'del_19q13.41' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 134 32.0 (9.3)
DEL PEAK 29(19Q13.41) MUTATED 47 28.8 (9.5)
DEL PEAK 29(19Q13.41) WILD-TYPE 87 33.7 (8.8)

Figure S3.  Get High-res Image Gene #44: 'del_19q13.41' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'del_19q13.41' versus 'PATHOLOGIC_STAGE'

P value = 4e-04 (Fisher's exact test), Q value = 0.082

Table S4.  Gene #44: 'del_19q13.41' versus Clinical Feature #3: 'PATHOLOGIC_STAGE'

nPatients STAGE I STAGE IA STAGE IB STAGE II STAGE IIA STAGE IIB STAGE IIC STAGE III STAGE IIIA STAGE IIIB STAGE IIIC STAGE IS
ALL 19 26 11 5 6 1 1 2 1 6 5 46
DEL PEAK 29(19Q13.41) MUTATED 3 3 3 5 4 0 0 1 0 4 3 19
DEL PEAK 29(19Q13.41) WILD-TYPE 16 23 8 0 2 1 1 1 1 2 2 27

Figure S4.  Get High-res Image Gene #44: 'del_19q13.41' versus Clinical Feature #3: 'PATHOLOGIC_STAGE'

'del_19q13.41' versus 'RADIATION_THERAPY'

P value = 0.000133 (Fisher's exact test), Q value = 0.063

Table S5.  Gene #44: 'del_19q13.41' versus Clinical Feature #7: 'RADIATION_THERAPY'

nPatients NO YES
ALL 110 19
DEL PEAK 29(19Q13.41) MUTATED 47 0
DEL PEAK 29(19Q13.41) WILD-TYPE 63 19

Figure S5.  Get High-res Image Gene #44: 'del_19q13.41' versus Clinical Feature #7: 'RADIATION_THERAPY'

Methods & Data
Input

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

  • Processed Copy number data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/TGCT-TP/19781845/transformed.cor.cli.txt

  • Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/TGCT-TP/19775566/TGCT-TP.merged_data.txt

  • Number of patients = 134

  • Number of significantly focal cnvs = 47

  • Number of selected clinical features = 10

  • 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

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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