Breast Invasive Carcinoma: Correlation between copy number variations of arm-level result and selected clinical features
Maintained by TCGA GDAC Team (Broad Institute/Dana-Farber Cancer Institute/Harvard Medical School)
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 80 arm-level results and 5 clinical features across 843 patients, one significant finding detected with Q value < 0.25.

  • 16q loss cnv correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 80 arm-level results and 5 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 GENDER RADIATIONS
RADIATION
REGIMENINDICATION 		NEOADJUVANT
THERAPY
nCNV (%) nWild-Type logrank test t-test Fisher's exact test Fisher's exact test Fisher's exact test
16q loss 363 (43%) 480 0.0227
(1.00) 		0.000497
(0.199) 		1
(1.00) 		0.565
(1.00) 		0.384
(1.00)
1p gain 91 (11%) 752 0.167
(1.00) 		0.347
(1.00) 		1
(1.00) 		0.0129
(1.00) 		0.0365
(1.00)
1q gain 449 (53%) 394 0.0707
(1.00) 		0.303
(1.00) 		1
(1.00) 		0.255
(1.00) 		0.829
(1.00)
2p gain 47 (6%) 796 0.785
(1.00) 		0.602
(1.00) 		1
(1.00) 		0.48
(1.00) 		0.755
(1.00)
2q gain 25 (3%) 818 0.972
(1.00) 		0.957
(1.00) 		1
(1.00) 		0.00656
(1.00) 		0.0928
(1.00)
3p gain 50 (6%) 793 0.846
(1.00) 		0.0911
(1.00) 		1
(1.00) 		0.61
(1.00) 		0.649
(1.00)
3q gain 94 (11%) 749 0.317
(1.00) 		0.857
(1.00) 		0.608
(1.00) 		1
(1.00) 		0.819
(1.00)
4p gain 29 (3%) 814 0.0672
(1.00) 		0.485
(1.00) 		1
(1.00) 		0.51
(1.00) 		0.433
(1.00)
4q gain 27 (3%) 816 0.0252
(1.00) 		0.359
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
5p gain 159 (19%) 684 0.107
(1.00) 		0.0427
(1.00) 		0.681
(1.00) 		0.0478
(1.00) 		0.142
(1.00)
5q gain 97 (12%) 746 0.332
(1.00) 		0.00255
(1.00) 		1
(1.00) 		0.125
(1.00) 		0.368
(1.00)
6p gain 93 (11%) 750 0.856
(1.00) 		0.145
(1.00) 		1
(1.00) 		0.00947
(1.00) 		0.207
(1.00)
6q gain 58 (7%) 785 0.266
(1.00) 		0.0595
(1.00) 		0.475
(1.00) 		0.631
(1.00) 		0.888
(1.00)
7p gain 151 (18%) 692 0.712
(1.00) 		0.129
(1.00) 		0.0118
(1.00) 		0.0259
(1.00) 		0.0248
(1.00)
7q gain 109 (13%) 734 0.461
(1.00) 		0.534
(1.00) 		0.0199
(1.00) 		0.0148
(1.00) 		0.00716
(1.00)
8p gain 158 (19%) 685 0.719
(1.00) 		0.104
(1.00) 		0.679
(1.00) 		0.835
(1.00) 		0.927
(1.00)
8q gain 358 (42%) 485 0.764
(1.00) 		0.0242
(1.00) 		0.506
(1.00) 		0.0481
(1.00) 		0.663
(1.00)
9p gain 65 (8%) 778 0.503
(1.00) 		0.526
(1.00) 		1
(1.00) 		0.285
(1.00) 		0.346
(1.00)
9q gain 52 (6%) 791 0.699
(1.00) 		0.287
(1.00) 		1
(1.00) 		0.0614
(1.00) 		0.459
(1.00)
10p gain 106 (13%) 737 0.804
(1.00) 		0.671
(1.00) 		0.612
(1.00) 		0.326
(1.00) 		0.516
(1.00)
10q gain 44 (5%) 799 0.731
(1.00) 		0.332
(1.00) 		1
(1.00) 		0.199
(1.00) 		0.0232
(1.00)
11p gain 62 (7%) 781 0.675
(1.00) 		0.857
(1.00) 		0.499
(1.00) 		0.641
(1.00) 		1
(1.00)
11q gain 44 (5%) 799 0.0485
(1.00) 		0.813
(1.00) 		1
(1.00) 		0.855
(1.00) 		1
(1.00)
12p gain 109 (13%) 734 0.759
(1.00) 		0.451
(1.00) 		0.0199
(1.00) 		0.276
(1.00) 		0.393
(1.00)
12q gain 83 (10%) 760 0.158
(1.00) 		0.118
(1.00) 		0.05
(1.00) 		0.34
(1.00) 		0.809
(1.00)
13q gain 44 (5%) 799 0.803
(1.00) 		0.94
(1.00) 		1
(1.00) 		0.583
(1.00) 		0.873
(1.00)
14q gain 75 (9%) 768 0.258
(1.00) 		0.513
(1.00) 		1
(1.00) 		0.319
(1.00) 		0.614
(1.00)
15q gain 44 (5%) 799 0.619
(1.00) 		0.84
(1.00) 		0.384
(1.00) 		0.199
(1.00) 		0.106
(1.00)
16p gain 235 (28%) 608 0.646
(1.00) 		0.0296
(1.00) 		1
(1.00) 		0.414
(1.00) 		0.297
(1.00)
16q gain 52 (6%) 791 0.0455
(1.00) 		0.806
(1.00) 		0.438
(1.00) 		1
(1.00) 		0.183
(1.00)
17p gain 45 (5%) 798 0.643
(1.00) 		0.449
(1.00) 		0.00953
(1.00) 		1
(1.00) 		0.752
(1.00)
17q gain 118 (14%) 725 0.812
(1.00) 		0.897
(1.00) 		0.0262
(1.00) 		0.815
(1.00) 		0.148
(1.00)
18p gain 81 (10%) 762 0.102
(1.00) 		0.0223
(1.00) 		0.599
(1.00) 		0.0373
(1.00) 		0.808
(1.00)
18q gain 71 (8%) 772 0.136
(1.00) 		0.415
(1.00) 		0.549
(1.00) 		0.142
(1.00) 		0.606
(1.00)
19p gain 67 (8%) 776 0.124
(1.00) 		0.178
(1.00) 		0.156
(1.00) 		0.07
(1.00) 		0.791
(1.00)
19q gain 82 (10%) 761 0.0193
(1.00) 		0.827
(1.00) 		0.215
(1.00) 		0.414
(1.00) 		0.904
(1.00)
20p gain 231 (27%) 612 0.0448
(1.00) 		0.0875
(1.00) 		0.069
(1.00) 		0.856
(1.00) 		0.747
(1.00)
20q gain 264 (31%) 579 0.14
(1.00) 		0.434
(1.00) 		0.148
(1.00) 		0.599
(1.00) 		0.816
(1.00)
21q gain 98 (12%) 745 0.0414
(1.00) 		0.0355
(1.00) 		1
(1.00) 		0.0429
(1.00) 		0.372
(1.00)
22q gain 38 (5%) 805 0.962
(1.00) 		0.353
(1.00) 		1
(1.00) 		0.559
(1.00) 		1
(1.00)
Xq gain 20 (2%) 823 0.119
(1.00) 		0.112
(1.00) 		1
(1.00) 		0.281
(1.00) 		1
(1.00)
1p loss 113 (13%) 730 0.303
(1.00) 		0.00889
(1.00) 		1
(1.00) 		0.34
(1.00) 		0.0912
(1.00)
1q loss 20 (2%) 823 0.987
(1.00) 		0.639
(1.00) 		1
(1.00) 		0.794
(1.00) 		0.814
(1.00)
2p loss 69 (8%) 774 0.69
(1.00) 		0.237
(1.00) 		1
(1.00) 		0.298
(1.00) 		0.6
(1.00)
2q loss 83 (10%) 760 0.54
(1.00) 		0.413
(1.00) 		1
(1.00) 		0.34
(1.00) 		0.905
(1.00)
3p loss 88 (10%) 755 0.0422
(1.00) 		0.0411
(1.00) 		0.609
(1.00) 		0.354
(1.00) 		0.639
(1.00)
3q loss 44 (5%) 799 0.267
(1.00) 		0.0692
(1.00) 		1
(1.00) 		0.0439
(1.00) 		0.747
(1.00)
4p loss 176 (21%) 667 0.455
(1.00) 		0.25
(1.00) 		1
(1.00) 		0.162
(1.00) 		0.0269
(1.00)
4q loss 147 (17%) 696 0.479
(1.00) 		0.891
(1.00) 		0.372
(1.00) 		0.284
(1.00) 		0.185
(1.00)
5p loss 68 (8%) 775 0.116
(1.00) 		0.0828
(1.00) 		0.533
(1.00) 		1
(1.00) 		0.187
(1.00)
5q loss 118 (14%) 725 0.413
(1.00) 		0.154
(1.00) 		0.621
(1.00) 		0.815
(1.00) 		0.0625
(1.00)
6p loss 107 (13%) 736 0.255
(1.00) 		0.074
(1.00) 		0.613
(1.00) 		0.223
(1.00) 		0.914
(1.00)
6q loss 164 (19%) 679 0.957
(1.00) 		0.00421
(1.00) 		0.219
(1.00) 		0.123
(1.00) 		0.651
(1.00)
7p loss 46 (5%) 797 0.526
(1.00) 		0.404
(1.00) 		1
(1.00) 		0.281
(1.00) 		0.528
(1.00)
7q loss 60 (7%) 783 0.229
(1.00) 		0.112
(1.00) 		1
(1.00) 		0.345
(1.00) 		0.78
(1.00)
8p loss 265 (31%) 578 0.00448
(1.00) 		0.521
(1.00) 		1
(1.00) 		0.661
(1.00) 		1
(1.00)
8q loss 42 (5%) 801 0.00363
(1.00) 		0.69
(1.00) 		1
(1.00) 		0.853
(1.00) 		0.621
(1.00)
9p loss 182 (22%) 661 0.00935
(1.00) 		0.911
(1.00) 		0.415
(1.00) 		0.553
(1.00) 		0.0553
(1.00)
9q loss 139 (16%) 704 0.0156
(1.00) 		0.637
(1.00) 		0.173
(1.00) 		1
(1.00) 		0.066
(1.00)
10p loss 70 (8%) 773 0.0717
(1.00) 		0.365
(1.00) 		1
(1.00) 		0.769
(1.00) 		0.241
(1.00)
10q loss 106 (13%) 737 0.0047
(1.00) 		0.645
(1.00) 		0.612
(1.00) 		0.714
(1.00) 		0.233
(1.00)
11p loss 135 (16%) 708 0.0285
(1.00) 		0.292
(1.00) 		0.368
(1.00) 		1
(1.00) 		0.241
(1.00)
11q loss 218 (26%) 625 0.282
(1.00) 		0.564
(1.00) 		0.055
(1.00) 		0.516
(1.00) 		0.46
(1.00)
12p loss 65 (8%) 778 0.0966
(1.00) 		0.93
(1.00) 		0.516
(1.00) 		0.647
(1.00) 		0.283
(1.00)
12q loss 50 (6%) 793 0.228
(1.00) 		0.183
(1.00) 		1
(1.00) 		0.49
(1.00) 		0.448
(1.00)
13q loss 253 (30%) 590 0.0807
(1.00) 		0.168
(1.00) 		0.464
(1.00) 		0.79
(1.00) 		0.754
(1.00)
14q loss 125 (15%) 718 0.00789
(1.00) 		0.177
(1.00) 		0.37
(1.00) 		0.82
(1.00) 		0.19
(1.00)
15q loss 153 (18%) 690 0.225
(1.00) 		0.159
(1.00) 		0.377
(1.00) 		0.398
(1.00) 		0.852
(1.00)
16p loss 52 (6%) 791 0.688
(1.00) 		0.971
(1.00) 		0.102
(1.00) 		1
(1.00) 		0.882
(1.00)
17p loss 352 (42%) 491 0.327
(1.00) 		0.0349
(1.00) 		0.742
(1.00) 		0.187
(1.00) 		0.275
(1.00)
17q loss 138 (16%) 705 0.616
(1.00) 		0.252
(1.00) 		0.369
(1.00) 		0.912
(1.00) 		0.561
(1.00)
18p loss 167 (20%) 676 0.0063
(1.00) 		0.00159
(0.63) 		1
(1.00) 		0.759
(1.00) 		0.928
(1.00)
18q loss 166 (20%) 677 0.0407
(1.00) 		0.00123
(0.491) 		1
(1.00) 		0.61
(1.00) 		0.47
(1.00)
19p loss 67 (8%) 776 0.569
(1.00) 		0.326
(1.00) 		1
(1.00) 		0.297
(1.00) 		0.507
(1.00)
19q loss 54 (6%) 789 0.901
(1.00) 		0.889
(1.00) 		1
(1.00) 		0.74
(1.00) 		0.559
(1.00)
20p loss 48 (6%) 795 0.00139
(0.553) 		0.826
(1.00) 		0.412
(1.00) 		1
(1.00) 		0.218
(1.00)
20q loss 25 (3%) 818 0.794
(1.00) 		0.922
(1.00) 		1
(1.00) 		0.814
(1.00) 		0.054
(1.00)
21q loss 84 (10%) 759 0.987
(1.00) 		0.718
(1.00) 		0.61
(1.00) 		1
(1.00) 		0.0558
(1.00)
22q loss 284 (34%) 559 0.122
(1.00) 		0.823
(1.00) 		0.173
(1.00) 		0.048
(1.00) 		0.939
(1.00)
Xq loss 31 (4%) 812 0.056
(1.00) 		0.585
(1.00) 		0.0401
(1.00) 		0.672
(1.00) 		1
(1.00)
'16q loss mutation analysis' versus 'AGE'

P value = 0.000497 (t-test), Q value = 0.2

Table S1.  Gene #69: '16q loss mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 842 58.5 (13.2)
16Q LOSS MUTATED 363 60.3 (12.9)
16Q LOSS WILD-TYPE 479 57.1 (13.3)

Figure S1.  Get High-res Image Gene #69: '16q loss mutation analysis' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

  • Mutation data file = broad_values_by_arm.mutsig.cluster.txt

  • Clinical data file = BRCA.clin.merged.picked.txt

  • Number of patients = 843

  • Number of significantly arm-level cnvs = 80

  • Number of selected clinical features = 5

  • 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

Student's t-test analysis

For continuous numerical clinical features, two-tailed Student's t test with unequal variance (Lehmann and Romano 2005) was applied to compare the clinical values between tumors with and without gene mutations using 't.test' 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

This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.

References
[1] Bland and Altman, Statistics notes: The logrank test, BMJ 328(7447):1073 (2004)
[2] Lehmann and Romano, Testing Statistical Hypotheses (3E ed.), New York: Springer. ISBN 0387988645 (2005)
[3] 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)
[4] 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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