Correlation between copy number variation genes (focal events) and selected clinical features
Sarcoma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C14F1PNZ
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 variation genes (focal events) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C14F1PNZ
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 66 focal events and 4 clinical features across 156 patients, 8 significant findings detected with Q value < 0.25.

  • amp_3p12.1 cnv correlated to 'AGE'.

  • amp_7q31.2 cnv correlated to 'AGE'.

  • amp_20q13.33 cnv correlated to 'AGE'.

  • del_2p25.3 cnv correlated to 'GENDER'.

  • del_11p15.5 cnv correlated to 'AGE'.

  • del_13q14.2 cnv correlated to 'AGE'.

  • del_19p13.3 cnv correlated to 'GENDER'.

  • del_21q22.3 cnv correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 66 focal events and 4 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 8 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER RACE
nCNV (%) nWild-Type logrank test Wilcoxon-test Fisher's exact test Fisher's exact test
amp 3p12 1 36 (23%) 120 0.482
(1.00) 		0.000586
(0.152) 		0.251
(1.00) 		1
(1.00)
amp 7q31 2 44 (28%) 112 0.175
(1.00) 		1.86e-05
(0.00491) 		0.858
(1.00) 		0.71
(1.00)
amp 20q13 33 62 (40%) 94 0.249
(1.00) 		0.000778
(0.201) 		0.0692
(1.00) 		0.907
(1.00)
del 2p25 3 55 (35%) 101 0.37
(1.00) 		0.18
(1.00) 		0.000205
(0.054) 		0.277
(1.00)
del 11p15 5 67 (43%) 89 0.573
(1.00) 		0.000505
(0.131) 		0.33
(1.00) 		0.702
(1.00)
del 13q14 2 112 (72%) 44 0.241
(1.00) 		0.000954
(0.245) 		0.0194
(1.00) 		0.48
(1.00)
del 19p13 3 47 (30%) 109 0.416
(1.00) 		0.977
(1.00) 		0.000213
(0.0557) 		0.743
(1.00)
del 21q22 3 45 (29%) 111 0.161
(1.00) 		0.00038
(0.0992) 		0.722
(1.00) 		0.812
(1.00)
amp 1p32 1 54 (35%) 102 0.0589
(1.00) 		0.00754
(1.00) 		0.735
(1.00) 		0.324
(1.00)
amp 1q21 3 57 (37%) 99 0.538
(1.00) 		0.0604
(1.00) 		0.132
(1.00) 		0.758
(1.00)
amp 1q24 3 66 (42%) 90 0.968
(1.00) 		0.142
(1.00) 		0.871
(1.00) 		0.829
(1.00)
amp 2p11 2 35 (22%) 121 0.846
(1.00) 		0.0431
(1.00) 		0.248
(1.00) 		0.031
(1.00)
amp 4q12 38 (24%) 118 0.302
(1.00) 		0.0564
(1.00) 		0.579
(1.00) 		0.115
(1.00)
amp 5p15 33 70 (45%) 86 0.127
(1.00) 		0.00228
(0.576) 		0.631
(1.00) 		0.831
(1.00)
amp 6p21 1 35 (22%) 121 0.0276
(1.00) 		0.00852
(1.00) 		0.442
(1.00) 		0.525
(1.00)
amp 6q25 1 47 (30%) 109 0.975
(1.00) 		0.0407
(1.00) 		0.224
(1.00) 		0.656
(1.00)
amp 8p11 22 49 (31%) 107 0.0268
(1.00) 		0.00296
(0.746) 		0.297
(1.00) 		0.0226
(1.00)
amp 8q24 21 49 (31%) 107 0.0779
(1.00) 		0.894
(1.00) 		0.488
(1.00) 		0.0468
(1.00)
amp 11q22 2 24 (15%) 132 0.0826
(1.00) 		0.301
(1.00) 		0.51
(1.00) 		0.525
(1.00)
amp 12q15 60 (38%) 96 0.251
(1.00) 		0.0854
(1.00) 		0.0126
(1.00) 		0.022
(1.00)
amp 13q34 29 (19%) 127 0.592
(1.00) 		0.736
(1.00) 		0.0226
(1.00) 		0.0372
(1.00)
amp 15q26 3 50 (32%) 106 0.203
(1.00) 		0.00951
(1.00) 		0.12
(1.00) 		0.258
(1.00)
amp 17p12 61 (39%) 95 0.661
(1.00) 		0.0387
(1.00) 		0.251
(1.00) 		0.572
(1.00)
amp 17p11 2 61 (39%) 95 0.399
(1.00) 		0.0508
(1.00) 		0.0326
(1.00) 		0.527
(1.00)
amp 17q24 3 46 (29%) 110 0.269
(1.00) 		0.0485
(1.00) 		0.00474
(1.00) 		0.36
(1.00)
amp 19p13 2 57 (37%) 99 0.662
(1.00) 		0.194
(1.00) 		0.318
(1.00) 		1
(1.00)
amp 19q12 54 (35%) 102 0.0499
(1.00) 		0.0014
(0.358) 		0.867
(1.00) 		0.665
(1.00)
amp 21q21 1 46 (29%) 110 0.208
(1.00) 		0.054
(1.00) 		0.215
(1.00) 		1
(1.00)
amp xp21 2 57 (37%) 99 0.72
(1.00) 		0.579
(1.00) 		0.616
(1.00) 		0.564
(1.00)
amp xq21 1 27 (17%) 129 0.107
(1.00) 		0.0343
(1.00) 		0.832
(1.00) 		0.397
(1.00)
del 1p36 32 47 (30%) 109 0.0132
(1.00) 		0.329
(1.00) 		0.0779
(1.00) 		1
(1.00)
del 1q44 44 (28%) 112 0.469
(1.00) 		0.0342
(1.00) 		0.477
(1.00) 		0.305
(1.00)
del 2q37 3 59 (38%) 97 0.0611
(1.00) 		0.27
(1.00) 		0.408
(1.00) 		0.758
(1.00)
del 2q37 3 62 (40%) 94 0.247
(1.00) 		0.0866
(1.00) 		0.328
(1.00) 		0.907
(1.00)
del 3p21 31 37 (24%) 119 0.759
(1.00) 		0.164
(1.00) 		0.708
(1.00) 		0.225
(1.00)
del 3q13 31 31 (20%) 125 0.0866
(1.00) 		0.00167
(0.424) 		0.843
(1.00) 		0.87
(1.00)
del 3q29 36 (23%) 120 0.555
(1.00) 		0.366
(1.00) 		0.702
(1.00) 		0.353
(1.00)
del 4q35 1 56 (36%) 100 0.177
(1.00) 		0.0108
(1.00) 		0.501
(1.00) 		0.131
(1.00)
del 5p15 33 20 (13%) 136 0.701
(1.00) 		0.563
(1.00) 		0.232
(1.00) 		0.815
(1.00)
del 6p25 3 50 (32%) 106 0.466
(1.00) 		0.247
(1.00) 		0.389
(1.00) 		0.665
(1.00)
del 6q14 1 44 (28%) 112 0.814
(1.00) 		0.212
(1.00) 		0.477
(1.00) 		1
(1.00)
del 7q36 3 44 (28%) 112 0.951
(1.00) 		0.561
(1.00) 		1
(1.00) 		0.223
(1.00)
del 8p23 3 46 (29%) 110 0.28
(1.00) 		0.283
(1.00) 		0.86
(1.00) 		0.897
(1.00)
del 9p24 3 59 (38%) 97 0.868
(1.00) 		0.00392
(0.983) 		0.246
(1.00) 		0.909
(1.00)
del 9p21 3 69 (44%) 87 0.657
(1.00) 		0.0115
(1.00) 		0.334
(1.00) 		0.201
(1.00)
del 9q34 3 38 (24%) 118 0.284
(1.00) 		0.147
(1.00) 		0.354
(1.00) 		0.196
(1.00)
del 10p15 3 80 (51%) 76 0.254
(1.00) 		0.089
(1.00) 		0.0755
(1.00) 		0.361
(1.00)
del 10q23 31 88 (56%) 68 0.419
(1.00) 		0.169
(1.00) 		0.00903
(1.00) 		0.0915
(1.00)
del 10q26 3 84 (54%) 72 0.59
(1.00) 		0.0566
(1.00) 		0.0157
(1.00) 		0.381
(1.00)
del 11q24 2 70 (45%) 86 0.722
(1.00) 		0.00552
(1.00) 		1
(1.00) 		0.481
(1.00)
del 12p13 1 53 (34%) 103 0.429
(1.00) 		0.259
(1.00) 		0.125
(1.00) 		0.596
(1.00)
del 12q12 34 (22%) 122 0.276
(1.00) 		0.608
(1.00) 		0.559
(1.00) 		0.485
(1.00)
del 12q24 33 44 (28%) 112 0.318
(1.00) 		0.0528
(1.00) 		0.591
(1.00) 		0.412
(1.00)
del 14q24 1 48 (31%) 108 0.179
(1.00) 		0.587
(1.00) 		0.382
(1.00) 		0.733
(1.00)
del 16q11 2 78 (50%) 78 0.748
(1.00) 		0.159
(1.00) 		0.0754
(1.00) 		0.202
(1.00)
del 16q23 1 85 (54%) 71 0.493
(1.00) 		0.00118
(0.302) 		0.0539
(1.00) 		0.472
(1.00)
del 17p13 1 74 (47%) 82 0.608
(1.00) 		0.488
(1.00) 		0.00967
(1.00) 		0.765
(1.00)
del 17q11 2 41 (26%) 115 0.356
(1.00) 		0.0659
(1.00) 		0.583
(1.00) 		1
(1.00)
del 17q25 3 40 (26%) 116 0.0527
(1.00) 		0.0425
(1.00) 		0.584
(1.00) 		1
(1.00)
del 18q23 49 (31%) 107 0.127
(1.00) 		0.00405
(1.00) 		0.164
(1.00) 		0.904
(1.00)
del 19q13 43 61 (39%) 95 0.881
(1.00) 		0.448
(1.00) 		0.251
(1.00) 		0.698
(1.00)
del 21q11 2 32 (21%) 124 0.344
(1.00) 		0.0956
(1.00) 		0.842
(1.00) 		0.669
(1.00)
del 22q13 32 52 (33%) 104 0.517
(1.00) 		0.274
(1.00) 		0.0607
(1.00) 		1
(1.00)
del xp21 1 36 (23%) 120 0.518
(1.00) 		0.634
(1.00) 		0.183
(1.00) 		0.535
(1.00)
del xq21 1 79 (51%) 77 0.0189
(1.00) 		0.268
(1.00) 		0.0523
(1.00) 		0.224
(1.00)
del xq22 3 78 (50%) 78 0.0718
(1.00) 		0.927
(1.00) 		0.146
(1.00) 		0.487
(1.00)
'amp_3p12.1' versus 'AGE'

P value = 0.000586 (Wilcoxon-test), Q value = 0.15

Table S1.  Gene #5: 'amp_3p12.1' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 156 61.5 (13.4)
AMP PEAK 5(3P12.1) MUTATED 36 68.4 (13.5)
AMP PEAK 5(3P12.1) WILD-TYPE 120 59.4 (12.8)

Figure S1.  Get High-res Image Gene #5: 'amp_3p12.1' versus Clinical Feature #2: 'AGE'

'amp_7q31.2' versus 'AGE'

P value = 1.86e-05 (Wilcoxon-test), Q value = 0.0049

Table S2.  Gene #10: 'amp_7q31.2' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 156 61.5 (13.4)
AMP PEAK 10(7Q31.2) MUTATED 44 68.4 (11.6)
AMP PEAK 10(7Q31.2) WILD-TYPE 112 58.8 (13.2)

Figure S2.  Get High-res Image Gene #10: 'amp_7q31.2' versus Clinical Feature #2: 'AGE'

'amp_20q13.33' versus 'AGE'

P value = 0.000778 (Wilcoxon-test), Q value = 0.2

Table S3.  Gene #22: 'amp_20q13.33' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 156 61.5 (13.4)
AMP PEAK 22(20Q13.33) MUTATED 62 66.1 (13.4)
AMP PEAK 22(20Q13.33) WILD-TYPE 94 58.5 (12.6)

Figure S3.  Get High-res Image Gene #22: 'amp_20q13.33' versus Clinical Feature #2: 'AGE'

'del_2p25.3' versus 'GENDER'

P value = 0.000205 (Fisher's exact test), Q value = 0.054

Table S4.  Gene #28: 'del_2p25.3' versus Clinical Feature #3: 'GENDER'

nPatients FEMALE MALE
ALL 88 68
DEL PEAK 3(2P25.3) MUTATED 42 13
DEL PEAK 3(2P25.3) WILD-TYPE 46 55

Figure S4.  Get High-res Image Gene #28: 'del_2p25.3' versus Clinical Feature #3: 'GENDER'

'del_11p15.5' versus 'AGE'

P value = 0.000505 (Wilcoxon-test), Q value = 0.13

Table S5.  Gene #46: 'del_11p15.5' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 156 61.5 (13.4)
DEL PEAK 21(11P15.5) MUTATED 67 65.6 (11.9)
DEL PEAK 21(11P15.5) WILD-TYPE 89 58.4 (13.7)

Figure S5.  Get High-res Image Gene #46: 'del_11p15.5' versus Clinical Feature #2: 'AGE'

'del_13q14.2' versus 'AGE'

P value = 0.000954 (Wilcoxon-test), Q value = 0.25

Table S6.  Gene #51: 'del_13q14.2' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 156 61.5 (13.4)
DEL PEAK 26(13Q14.2) MUTATED 112 63.7 (12.5)
DEL PEAK 26(13Q14.2) WILD-TYPE 44 56.0 (14.4)

Figure S6.  Get High-res Image Gene #51: 'del_13q14.2' versus Clinical Feature #2: 'AGE'

'del_19p13.3' versus 'GENDER'

P value = 0.000213 (Fisher's exact test), Q value = 0.056

Table S7.  Gene #59: 'del_19p13.3' versus Clinical Feature #3: 'GENDER'

nPatients FEMALE MALE
ALL 88 68
DEL PEAK 34(19P13.3) MUTATED 37 10
DEL PEAK 34(19P13.3) WILD-TYPE 51 58

Figure S7.  Get High-res Image Gene #59: 'del_19p13.3' versus Clinical Feature #3: 'GENDER'

'del_21q22.3' versus 'AGE'

P value = 0.00038 (Wilcoxon-test), Q value = 0.099

Table S8.  Gene #62: 'del_21q22.3' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 156 61.5 (13.4)
DEL PEAK 37(21Q22.3) MUTATED 45 67.4 (11.6)
DEL PEAK 37(21Q22.3) WILD-TYPE 111 59.1 (13.4)

Figure S8.  Get High-res Image Gene #62: 'del_21q22.3' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

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

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

  • Number of patients = 156

  • Number of significantly focal cnvs = 66

  • Number of selected clinical features = 4

  • 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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