Correlation between copy number variation genes (focal) and selected clinical features
Breast Invasive Carcinoma (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1MS3QNX
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Breast Invasive Carcinoma (Primary solid tumor cohort) - 21 April 2013: Correlation between copy number variation genes (focal) and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1MS3QNX
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 64 arm-level results and 9 clinical features across 857 patients, 3 significant findings detected with Q value < 0.25.

  • Amp Peak 24(17q23.1) cnv correlated to 'GENDER'.

  • Del Peak 4(3p14.3) cnv correlated to 'AGE'.

  • Del Peak 11(6q27) cnv correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 64 arm-level results and 9 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER RADIATIONS
RADIATION
REGIMENINDICATION 		DISTANT
METASTASIS 		LYMPH
NODE
METASTASIS 		NUMBER
OF
LYMPH
NODES 		TUMOR
STAGECODE 		NEOPLASM
DISEASESTAGE
nCNV (%) nWild-Type logrank test t-test Fisher's exact test Fisher's exact test Fisher's exact test Chi-square test t-test t-test Chi-square test
Amp Peak 24(17q23 1) 0 (0%) 500 0.069
(1.00) 		0.813
(1.00) 		0.000356
(0.182) 		0.422
(1.00) 		0.208
(1.00) 		0.435
(1.00) 		0.746
(1.00) 		0.0522
(1.00)
Del Peak 4(3p14 3) 0 (0%) 589 0.0193
(1.00) 		0.000136
(0.0696) 		1
(1.00) 		0.67
(1.00) 		0.691
(1.00) 		0.852
(1.00) 		0.986
(1.00) 		0.831
(1.00)
Del Peak 11(6q27) 0 (0%) 560 0.188
(1.00) 		0.000223
(0.114) 		0.174
(1.00) 		0.803
(1.00) 		0.191
(1.00) 		0.44
(1.00) 		0.389
(1.00) 		0.633
(1.00)
Amp Peak 1(1p22 3) 0 (0%) 669 0.987
(1.00) 		0.827
(1.00) 		1
(1.00) 		0.775
(1.00) 		0.909
(1.00) 		0.347
(1.00) 		0.103
(1.00) 		0.482
(1.00)
Amp Peak 2(1q21 3) 0 (0%) 242 0.81
(1.00) 		0.471
(1.00) 		0.28
(1.00) 		0.187
(1.00) 		0.739
(1.00) 		0.19
(1.00) 		0.691
(1.00) 		0.185
(1.00)
Amp Peak 3(1q44) 0 (0%) 244 0.0122
(1.00) 		0.884
(1.00) 		0.719
(1.00) 		0.381
(1.00) 		0.185
(1.00) 		0.14
(1.00) 		0.758
(1.00) 		0.112
(1.00)
Amp Peak 4(3p26 1) 0 (0%) 675 0.00505
(1.00) 		0.64
(1.00) 		0.217
(1.00) 		0.847
(1.00) 		0.13
(1.00) 		0.275
(1.00) 		0.582
(1.00) 		0.066
(1.00)
Amp Peak 5(3q26 32) 0 (0%) 580 0.621
(1.00) 		0.338
(1.00) 		0.726
(1.00) 		0.127
(1.00) 		0.273
(1.00) 		0.928
(1.00) 		0.769
(1.00) 		0.139
(1.00)
Amp Peak 6(4q13 3) 0 (0%) 718 0.00214
(1.00) 		0.369
(1.00) 		1
(1.00) 		0.915
(1.00) 		0.431
(1.00) 		0.179
(1.00) 		0.329
(1.00) 		0.0242
(1.00)
Amp Peak 7(6p23) 0 (0%) 630 0.63
(1.00) 		0.287
(1.00) 		0.458
(1.00) 		0.243
(1.00) 		1
(1.00) 		0.334
(1.00) 		0.273
(1.00) 		0.467
(1.00)
Amp Peak 8(6q21) 0 (0%) 698 0.0125
(1.00) 		0.562
(1.00) 		1
(1.00) 		0.611
(1.00) 		0.942
(1.00) 		0.453
(1.00) 		0.944
(1.00) 		0.211
(1.00)
Amp Peak 9(8p11 23) 0 (0%) 527 0.0287
(1.00) 		0.122
(1.00) 		0.165
(1.00) 		0.515
(1.00) 		0.491
(1.00) 		0.0498
(1.00) 		0.0123
(1.00) 		0.0226
(1.00)
Amp Peak 10(8p11 21) 0 (0%) 524 0.836
(1.00) 		0.058
(1.00) 		0.165
(1.00) 		0.0285
(1.00) 		0.632
(1.00) 		0.467
(1.00) 		0.554
(1.00) 		0.101
(1.00)
Amp Peak 11(8q24 21) 0 (0%) 299 0.12
(1.00) 		0.128
(1.00) 		0.507
(1.00) 		0.561
(1.00) 		0.376
(1.00) 		0.00627
(1.00) 		0.19
(1.00) 		0.239
(1.00)
Amp Peak 12(10p15 1) 0 (0%) 611 0.201
(1.00) 		0.733
(1.00) 		0.0665
(1.00) 		0.294
(1.00) 		0.932
(1.00) 		0.884
(1.00) 		0.976
(1.00) 		0.139
(1.00)
Amp Peak 13(10q22 3) 0 (0%) 728 0.115
(1.00) 		0.774
(1.00) 		1
(1.00) 		0.507
(1.00) 		0.0973
(1.00) 		0.497
(1.00) 		0.693
(1.00) 		0.266
(1.00)
Amp Peak 14(11p13) 0 (0%) 673 0.465
(1.00) 		0.695
(1.00) 		1
(1.00) 		0.501
(1.00) 		0.729
(1.00) 		0.32
(1.00) 		0.804
(1.00) 		0.252
(1.00)
Amp Peak 15(11q13 3) 0 (0%) 526 0.236
(1.00) 		0.267
(1.00) 		0.319
(1.00) 		0.745
(1.00) 		0.66
(1.00) 		0.509
(1.00) 		0.397
(1.00) 		0.611
(1.00)
Amp Peak 16(11q14 1) 0 (0%) 633 0.193
(1.00) 		0.241
(1.00) 		0.704
(1.00) 		0.719
(1.00) 		0.615
(1.00) 		0.44
(1.00) 		0.372
(1.00) 		0.938
(1.00)
Amp Peak 17(12p13 33) 0 (0%) 633 0.796
(1.00) 		0.552
(1.00) 		0.459
(1.00) 		0.0875
(1.00) 		0.501
(1.00) 		0.141
(1.00) 		0.782
(1.00) 		0.149
(1.00)
Amp Peak 18(12q15) 0 (0%) 630 0.0398
(1.00) 		0.329
(1.00) 		0.013
(1.00) 		0.721
(1.00) 		0.299
(1.00) 		0.126
(1.00) 		0.197
(1.00) 		0.153
(1.00)
Amp Peak 19(13q12 3) 0 (0%) 732 0.0381
(1.00) 		0.274
(1.00) 		0.627
(1.00) 		0.502
(1.00) 		0.475
(1.00) 		0.329
(1.00) 		0.617
(1.00) 		0.577
(1.00)
Amp Peak 20(13q34) 0 (0%) 708 0.988
(1.00) 		0.106
(1.00) 		0.372
(1.00) 		0.917
(1.00) 		0.649
(1.00) 		0.00341
(1.00) 		0.819
(1.00) 		0.0471
(1.00)
Amp Peak 21(14q21 1) 0 (0%) 680 0.424
(1.00) 		0.041
(1.00) 		0.694
(1.00) 		0.626
(1.00) 		0.933
(1.00) 		0.0892
(1.00) 		0.048
(1.00) 		0.0126
(1.00)
Amp Peak 22(15q26 3) 0 (0%) 696 0.209
(1.00) 		0.0322
(1.00) 		0.0694
(1.00) 		0.613
(1.00) 		0.194
(1.00) 		0.933
(1.00) 		0.558
(1.00) 		0.808
(1.00)
Amp Peak 23(17q12) 0 (0%) 576 0.178
(1.00) 		0.639
(1.00) 		0.000802
(0.408) 		1
(1.00) 		0.586
(1.00) 		0.0842
(1.00) 		0.354
(1.00) 		0.314
(1.00)
Amp Peak 25(19q12) 0 (0%) 639 0.396
(1.00) 		0.518
(1.00) 		0.7
(1.00) 		0.103
(1.00) 		0.212
(1.00) 		0.0686
(1.00) 		0.483
(1.00) 		0.189
(1.00)
Amp Peak 26(19q13 42) 0 (0%) 629 0.64
(1.00) 		0.243
(1.00) 		0.257
(1.00) 		0.421
(1.00) 		0.141
(1.00) 		0.538
(1.00) 		0.817
(1.00) 		0.899
(1.00)
Amp Peak 27(20q13 2) 0 (0%) 410 0.693
(1.00) 		0.3
(1.00) 		0.181
(1.00) 		0.0571
(1.00) 		0.321
(1.00) 		0.508
(1.00) 		0.355
(1.00) 		0.486
(1.00)
Del Peak 1(1p36 13) 0 (0%) 494 0.205
(1.00) 		0.416
(1.00) 		0.179
(1.00) 		0.936
(1.00) 		0.636
(1.00) 		0.0817
(1.00) 		0.0317
(1.00) 		0.0731
(1.00)
Del Peak 2(1p22 1) 0 (0%) 563 0.00247
(1.00) 		0.189
(1.00) 		0.502
(1.00) 		0.157
(1.00) 		0.812
(1.00) 		0.00816
(1.00) 		0.0184
(1.00) 		0.0058
(1.00)
Del Peak 3(2q37 3) 0 (0%) 604 0.893
(1.00) 		0.931
(1.00) 		0.295
(1.00) 		0.488
(1.00) 		0.698
(1.00) 		0.464
(1.00) 		0.533
(1.00) 		0.535
(1.00)
Del Peak 5(4p16 3) 0 (0%) 589 0.824
(1.00) 		0.102
(1.00) 		0.728
(1.00) 		0.67
(1.00) 		0.841
(1.00) 		0.47
(1.00) 		0.791
(1.00) 		0.258
(1.00)
Del Peak 6(4q35 2) 0 (0%) 587 0.11
(1.00) 		0.793
(1.00) 		0.286
(1.00) 		1
(1.00) 		0.233
(1.00) 		0.128
(1.00) 		0.96
(1.00) 		0.486
(1.00)
Del Peak 7(5q11 2) 0 (0%) 635 0.228
(1.00) 		0.0105
(1.00) 		0.46
(1.00) 		0.527
(1.00) 		0.583
(1.00) 		0.688
(1.00) 		0.295
(1.00) 		0.638
(1.00)
Del Peak 8(5q21 3) 0 (0%) 644 0.343
(1.00) 		0.0208
(1.00) 		0.122
(1.00) 		1
(1.00) 		0.799
(1.00) 		0.458
(1.00) 		0.000851
(0.432) 		0.338
(1.00)
Del Peak 9(6p25 3) 0 (0%) 695 0.566
(1.00) 		0.0553
(1.00) 		0.681
(1.00) 		0.188
(1.00) 		0.795
(1.00) 		0.344
(1.00) 		0.0269
(1.00) 		0.607
(1.00)
Del Peak 10(6q15) 0 (0%) 568 0.415
(1.00) 		0.113
(1.00) 		0.726
(1.00) 		0.738
(1.00) 		0.421
(1.00) 		0.503
(1.00) 		0.141
(1.00) 		0.444
(1.00)
Del Peak 12(7p22 3) 0 (0%) 742 0.106
(1.00) 		0.271
(1.00) 		0.617
(1.00) 		0.728
(1.00) 		0.79
(1.00) 		0.823
(1.00) 		0.0365
(1.00) 		0.00602
(1.00)
Del Peak 13(7q36 1) 0 (0%) 684 0.0177
(1.00) 		0.871
(1.00) 		1
(1.00) 		0.279
(1.00) 		0.254
(1.00) 		0.8
(1.00) 		0.823
(1.00) 		0.839
(1.00)
Del Peak 14(8p23 2) 0 (0%) 401 0.277
(1.00) 		0.679
(1.00) 		0.514
(1.00) 		0.178
(1.00) 		0.432
(1.00) 		0.0927
(1.00) 		0.725
(1.00) 		0.987
(1.00)
Del Peak 15(8p11 21) 0 (0%) 691 0.0148
(1.00) 		0.386
(1.00) 		0.219
(1.00) 		0.764
(1.00) 		0.654
(1.00) 		0.0466
(1.00) 		0.216
(1.00) 		0.379
(1.00)
Del Peak 16(9p21 3) 0 (0%) 561 0.0308
(1.00) 		0.686
(1.00) 		0.288
(1.00) 		0.183
(1.00) 		0.751
(1.00) 		0.0026
(1.00) 		0.115
(1.00) 		0.0102
(1.00)
Del Peak 17(9q21 11) 0 (0%) 620 0.508
(1.00) 		0.869
(1.00) 		0.271
(1.00) 		0.86
(1.00) 		0.387
(1.00) 		0.239
(1.00) 		0.62
(1.00) 		0.303
(1.00)
Del Peak 18(10q23 31) 0 (0%) 610 0.875
(1.00) 		0.611
(1.00) 		0.0662
(1.00) 		0.541
(1.00) 		0.791
(1.00) 		0.449
(1.00) 		0.841
(1.00) 		0.263
(1.00)
Del Peak 19(10q26 3) 0 (0%) 605 0.0442
(1.00) 		0.935
(1.00) 		0.296
(1.00) 		0.795
(1.00) 		0.309
(1.00) 		0.393
(1.00) 		0.565
(1.00) 		0.108
(1.00)
Del Peak 20(11p15 5) 0 (0%) 607 0.266
(1.00) 		0.849
(1.00) 		0.295
(1.00) 		0.931
(1.00) 		0.925
(1.00) 		0.878
(1.00) 		0.106
(1.00) 		0.751
(1.00)
Del Peak 21(11q13 1) 0 (0%) 674 0.36
(1.00) 		0.988
(1.00) 		0.411
(1.00) 		0.563
(1.00) 		0.692
(1.00) 		0.186
(1.00) 		0.592
(1.00) 		0.376
(1.00)
Del Peak 22(11q23 2) 0 (0%) 430 0.356
(1.00) 		0.373
(1.00) 		0.107
(1.00) 		0.937
(1.00) 		0.243
(1.00) 		0.201
(1.00) 		0.491
(1.00) 		0.235
(1.00)
Del Peak 23(11q25) 0 (0%) 457 0.202
(1.00) 		0.0201
(1.00) 		0.0906
(1.00) 		0.527
(1.00) 		0.376
(1.00) 		0.473
(1.00) 		0.532
(1.00) 		0.0803
(1.00)
Del Peak 24(12p13 1) 0 (0%) 706 0.578
(1.00) 		0.648
(1.00) 		0.663
(1.00) 		0.407
(1.00) 		0.17
(1.00) 		0.905
(1.00) 		0.574
(1.00) 		0.588
(1.00)
Del Peak 25(12q24 21) 0 (0%) 700 0.475
(1.00) 		0.227
(1.00) 		1
(1.00) 		0.759
(1.00) 		0.944
(1.00) 		0.517
(1.00) 		0.141
(1.00) 		0.846
(1.00)
Del Peak 26(13q14 2) 0 (0%) 461 0.066
(1.00) 		0.688
(1.00) 		0.74
(1.00) 		0.751
(1.00) 		0.959
(1.00) 		0.388
(1.00) 		0.169
(1.00) 		0.998
(1.00)
Del Peak 27(14q24 3) 0 (0%) 581 0.178
(1.00) 		0.838
(1.00) 		1
(1.00) 		0.446
(1.00) 		0.833
(1.00) 		0.1
(1.00) 		0.763
(1.00) 		0.518
(1.00)
Del Peak 28(15q13 1) 0 (0%) 557 0.41
(1.00) 		0.252
(1.00) 		1
(1.00) 		0.678
(1.00) 		0.436
(1.00) 		0.252
(1.00) 		0.787
(1.00) 		0.158
(1.00)
Del Peak 29(16q24 3) 0 (0%) 304 0.116
(1.00) 		0.000958
(0.485) 		1
(1.00) 		0.563
(1.00) 		0.448
(1.00) 		0.544
(1.00) 		0.435
(1.00) 		0.423
(1.00)
Del Peak 30(17p12) 0 (0%) 338 0.149
(1.00) 		0.00333
(1.00) 		0.495
(1.00) 		0.627
(1.00) 		0.874
(1.00) 		0.0094
(1.00) 		0.231
(1.00) 		0.745
(1.00)
Del Peak 31(17q21 31) 0 (0%) 556 0.587
(1.00) 		0.000695
(0.354) 		0.172
(1.00) 		0.868
(1.00) 		0.534
(1.00) 		0.306
(1.00) 		0.114
(1.00) 		0.807
(1.00)
Del Peak 32(18q23) 0 (0%) 578 0.022
(1.00) 		0.525
(1.00) 		1
(1.00) 		0.238
(1.00) 		0.505
(1.00) 		0.042
(1.00) 		0.165
(1.00) 		0.211
(1.00)
Del Peak 33(19p13 3) 0 (0%) 561 0.41
(1.00) 		0.032
(1.00) 		0.726
(1.00) 		0.74
(1.00) 		0.774
(1.00) 		0.433
(1.00) 		0.2
(1.00) 		0.699
(1.00)
Del Peak 34(19q13 32) 0 (0%) 680 0.854
(1.00) 		0.703
(1.00) 		0.694
(1.00) 		0.696
(1.00) 		0.168
(1.00) 		0.309
(1.00) 		0.931
(1.00) 		0.382
(1.00)
Del Peak 35(20p13) 0 (0%) 729 0.0126
(1.00) 		0.409
(1.00) 		0.63
(1.00) 		0.581
(1.00) 		0.688
(1.00) 		0.828
(1.00) 		0.796
(1.00) 		0.241
(1.00)
Del Peak 36(21q11 2) 0 (0%) 681 0.333
(1.00) 		0.477
(1.00) 		0.217
(1.00) 		0.239
(1.00) 		0.526
(1.00) 		0.556
(1.00) 		0.693
(1.00) 		0.0405
(1.00)
Del Peak 37(22q13 32) 0 (0%) 471 0.495
(1.00) 		0.647
(1.00) 		0.739
(1.00) 		0.0679
(1.00) 		0.864
(1.00) 		0.124
(1.00) 		0.814
(1.00) 		0.712
(1.00)
'Amp Peak 24(17q23.1)' versus 'GENDER'

P value = 0.000356 (Fisher's exact test), Q value = 0.18

Table S1.  Gene #24: 'Amp Peak 24(17q23.1)' versus Clinical Feature #3: 'GENDER'

nPatients FEMALE MALE
ALL 848 9
AMP PEAK 24(17Q23.1) CNV 348 9
AMP PEAK 24(17Q23.1) WILD-TYPE 500 0

Figure S1.  Get High-res Image Gene #24: 'Amp Peak 24(17q23.1)' versus Clinical Feature #3: 'GENDER'

'Del Peak 4(3p14.3)' versus 'AGE'

P value = 0.000136 (t-test), Q value = 0.07

Table S2.  Gene #31: 'Del Peak 4(3p14.3)' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 856 58.5 (13.2)
DEL PEAK 4(3P14.3) CNV 268 55.9 (13.1)
DEL PEAK 4(3P14.3) WILD-TYPE 588 59.6 (13.1)

Figure S2.  Get High-res Image Gene #31: 'Del Peak 4(3p14.3)' versus Clinical Feature #2: 'AGE'

'Del Peak 11(6q27)' versus 'AGE'

P value = 0.000223 (t-test), Q value = 0.11

Table S3.  Gene #38: 'Del Peak 11(6q27)' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 856 58.5 (13.2)
DEL PEAK 11(6Q27) CNV 297 56.2 (12.8)
DEL PEAK 11(6Q27) WILD-TYPE 559 59.7 (13.3)

Figure S3.  Get High-res Image Gene #38: 'Del Peak 11(6q27)' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

  • Mutation data file = all_lesions.conf_99.cnv.cluster.txt

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

  • Number of patients = 857

  • Number of significantly arm-level cnvs = 64

  • Number of selected clinical features = 9

  • 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

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[5] 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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