Breast Invasive Carcinoma: Correlation between copy number variation genes (focal) and selected clinical features
(primary solid tumor cohort)
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
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) 357 (42%) 500 0.069
(1.00) 		0.813
(1.00) 		0.000356
(0.182) 		0.422
(1.00) 		0.103
(1.00) 		0.477
(1.00) 		0.746
(1.00) 		0.0383
(1.00)
Del Peak 4(3p14 3) 268 (31%) 589 0.0193
(1.00) 		0.000136
(0.0696) 		1
(1.00) 		0.67
(1.00) 		0.423
(1.00) 		0.728
(1.00) 		0.986
(1.00) 		0.726
(1.00)
Del Peak 11(6q27) 297 (35%) 560 0.188
(1.00) 		0.000223
(0.114) 		0.174
(1.00) 		0.803
(1.00) 		0.231
(1.00) 		0.278
(1.00) 		0.389
(1.00) 		0.679
(1.00)
Amp Peak 1(1p22 3) 188 (22%) 669 0.987
(1.00) 		0.827
(1.00) 		1
(1.00) 		0.775
(1.00) 		0.58
(1.00) 		0.403
(1.00) 		0.103
(1.00) 		0.605
(1.00)
Amp Peak 2(1q21 3) 615 (72%) 242 0.81
(1.00) 		0.471
(1.00) 		0.28
(1.00) 		0.187
(1.00) 		0.469
(1.00) 		0.479
(1.00) 		0.691
(1.00) 		0.396
(1.00)
Amp Peak 3(1q44) 613 (72%) 244 0.0122
(1.00) 		0.884
(1.00) 		0.719
(1.00) 		0.381
(1.00) 		0.456
(1.00) 		0.239
(1.00) 		0.758
(1.00) 		0.504
(1.00)
Amp Peak 4(3p26 1) 182 (21%) 675 0.00505
(1.00) 		0.64
(1.00) 		0.217
(1.00) 		0.847
(1.00) 		0.0674
(1.00) 		0.129
(1.00) 		0.582
(1.00) 		0.114
(1.00)
Amp Peak 5(3q26 32) 277 (32%) 580 0.621
(1.00) 		0.338
(1.00) 		0.726
(1.00) 		0.127
(1.00) 		0.262
(1.00) 		0.87
(1.00) 		0.769
(1.00) 		0.553
(1.00)
Amp Peak 6(4q13 3) 139 (16%) 718 0.00214
(1.00) 		0.369
(1.00) 		1
(1.00) 		0.915
(1.00) 		0.816
(1.00) 		0.298
(1.00) 		0.329
(1.00) 		0.279
(1.00)
Amp Peak 7(6p23) 227 (26%) 630 0.63
(1.00) 		0.287
(1.00) 		0.458
(1.00) 		0.243
(1.00) 		0.929
(1.00) 		0.127
(1.00) 		0.273
(1.00) 		0.561
(1.00)
Amp Peak 8(6q21) 159 (19%) 698 0.0125
(1.00) 		0.562
(1.00) 		1
(1.00) 		0.611
(1.00) 		1
(1.00) 		0.818
(1.00) 		0.944
(1.00) 		0.362
(1.00)
Amp Peak 9(8p11 23) 330 (39%) 527 0.0287
(1.00) 		0.122
(1.00) 		0.165
(1.00) 		0.515
(1.00) 		0.077
(1.00) 		0.188
(1.00) 		0.0123
(1.00) 		0.0265
(1.00)
Amp Peak 10(8p11 21) 333 (39%) 524 0.836
(1.00) 		0.058
(1.00) 		0.165
(1.00) 		0.0285
(1.00) 		0.737
(1.00) 		0.532
(1.00) 		0.554
(1.00) 		0.415
(1.00)
Amp Peak 11(8q24 21) 558 (65%) 299 0.12
(1.00) 		0.128
(1.00) 		0.507
(1.00) 		0.561
(1.00) 		0.429
(1.00) 		0.0467
(1.00) 		0.19
(1.00) 		0.41
(1.00)
Amp Peak 12(10p15 1) 246 (29%) 611 0.201
(1.00) 		0.733
(1.00) 		0.0665
(1.00) 		0.294
(1.00) 		0.903
(1.00) 		0.828
(1.00) 		0.976
(1.00) 		0.527
(1.00)
Amp Peak 13(10q22 3) 129 (15%) 728 0.115
(1.00) 		0.774
(1.00) 		1
(1.00) 		0.507
(1.00) 		0.17
(1.00) 		0.669
(1.00) 		0.693
(1.00) 		0.328
(1.00)
Amp Peak 14(11p13) 184 (21%) 673 0.465
(1.00) 		0.695
(1.00) 		1
(1.00) 		0.501
(1.00) 		0.584
(1.00) 		0.522
(1.00) 		0.804
(1.00) 		0.347
(1.00)
Amp Peak 15(11q13 3) 331 (39%) 526 0.236
(1.00) 		0.267
(1.00) 		0.319
(1.00) 		0.745
(1.00) 		0.579
(1.00) 		0.683
(1.00) 		0.397
(1.00) 		0.273
(1.00)
Amp Peak 16(11q14 1) 224 (26%) 633 0.193
(1.00) 		0.241
(1.00) 		0.704
(1.00) 		0.719
(1.00) 		0.358
(1.00) 		0.726
(1.00) 		0.372
(1.00) 		0.267
(1.00)
Amp Peak 17(12p13 33) 224 (26%) 633 0.796
(1.00) 		0.552
(1.00) 		0.459
(1.00) 		0.0875
(1.00) 		0.734
(1.00) 		0.282
(1.00) 		0.782
(1.00) 		0.266
(1.00)
Amp Peak 18(12q15) 227 (26%) 630 0.0398
(1.00) 		0.329
(1.00) 		0.013
(1.00) 		0.721
(1.00) 		0.317
(1.00) 		0.056
(1.00) 		0.197
(1.00) 		0.131
(1.00)
Amp Peak 19(13q12 3) 125 (15%) 732 0.0381
(1.00) 		0.274
(1.00) 		0.627
(1.00) 		0.502
(1.00) 		0.213
(1.00) 		0.177
(1.00) 		0.617
(1.00) 		0.529
(1.00)
Amp Peak 20(13q34) 149 (17%) 708 0.988
(1.00) 		0.106
(1.00) 		0.372
(1.00) 		0.917
(1.00) 		0.457
(1.00) 		0.163
(1.00) 		0.819
(1.00) 		0.167
(1.00)
Amp Peak 21(14q21 1) 177 (21%) 680 0.424
(1.00) 		0.041
(1.00) 		0.694
(1.00) 		0.626
(1.00) 		0.593
(1.00) 		0.011
(1.00) 		0.048
(1.00) 		0.0372
(1.00)
Amp Peak 22(15q26 3) 161 (19%) 696 0.209
(1.00) 		0.0322
(1.00) 		0.0694
(1.00) 		0.613
(1.00) 		0.161
(1.00) 		0.708
(1.00) 		0.558
(1.00) 		0.717
(1.00)
Amp Peak 23(17q12) 281 (33%) 576 0.178
(1.00) 		0.639
(1.00) 		0.000802
(0.407) 		1
(1.00) 		0.608
(1.00) 		0.0378
(1.00) 		0.354
(1.00) 		0.197
(1.00)
Amp Peak 25(19q12) 218 (25%) 639 0.396
(1.00) 		0.518
(1.00) 		0.7
(1.00) 		0.103
(1.00) 		0.129
(1.00) 		0.0946
(1.00) 		0.483
(1.00) 		0.605
(1.00)
Amp Peak 26(19q13 42) 228 (27%) 629 0.64
(1.00) 		0.243
(1.00) 		0.257
(1.00) 		0.421
(1.00) 		0.125
(1.00) 		0.561
(1.00) 		0.817
(1.00) 		0.973
(1.00)
Amp Peak 27(20q13 2) 447 (52%) 410 0.693
(1.00) 		0.3
(1.00) 		0.181
(1.00) 		0.0571
(1.00) 		0.496
(1.00) 		0.245
(1.00) 		0.355
(1.00) 		0.304
(1.00)
Del Peak 1(1p36 13) 363 (42%) 494 0.205
(1.00) 		0.416
(1.00) 		0.179
(1.00) 		0.936
(1.00) 		0.366
(1.00) 		0.0637
(1.00) 		0.0317
(1.00) 		0.0274
(1.00)
Del Peak 2(1p22 1) 294 (34%) 563 0.00247
(1.00) 		0.189
(1.00) 		0.502
(1.00) 		0.157
(1.00) 		0.607
(1.00) 		0.00758
(1.00) 		0.0184
(1.00) 		0.0111
(1.00)
Del Peak 3(2q37 3) 253 (30%) 604 0.893
(1.00) 		0.931
(1.00) 		0.295
(1.00) 		0.488
(1.00) 		0.588
(1.00) 		0.452
(1.00) 		0.533
(1.00) 		0.617
(1.00)
Del Peak 5(4p16 3) 268 (31%) 589 0.824
(1.00) 		0.102
(1.00) 		0.728
(1.00) 		0.67
(1.00) 		0.907
(1.00) 		0.852
(1.00) 		0.791
(1.00) 		0.481
(1.00)
Del Peak 6(4q35 2) 270 (32%) 587 0.11
(1.00) 		0.793
(1.00) 		0.286
(1.00) 		1
(1.00) 		0.229
(1.00) 		0.485
(1.00) 		0.96
(1.00) 		0.906
(1.00)
Del Peak 7(5q11 2) 222 (26%) 635 0.228
(1.00) 		0.0105
(1.00) 		0.46
(1.00) 		0.527
(1.00) 		0.357
(1.00) 		0.605
(1.00) 		0.295
(1.00) 		0.619
(1.00)
Del Peak 8(5q21 3) 213 (25%) 644 0.343
(1.00) 		0.0208
(1.00) 		0.122
(1.00) 		1
(1.00) 		0.718
(1.00) 		0.278
(1.00) 		0.000851
(0.431) 		0.386
(1.00)
Del Peak 9(6p25 3) 162 (19%) 695 0.566
(1.00) 		0.0553
(1.00) 		0.681
(1.00) 		0.188
(1.00) 		0.765
(1.00) 		0.425
(1.00) 		0.0269
(1.00) 		0.688
(1.00)
Del Peak 10(6q15) 289 (34%) 568 0.415
(1.00) 		0.113
(1.00) 		0.726
(1.00) 		0.738
(1.00) 		0.554
(1.00) 		0.49
(1.00) 		0.141
(1.00) 		0.274
(1.00)
Del Peak 12(7p22 3) 115 (13%) 742 0.106
(1.00) 		0.271
(1.00) 		0.617
(1.00) 		0.728
(1.00) 		0.828
(1.00) 		0.832
(1.00) 		0.0365
(1.00) 		0.0952
(1.00)
Del Peak 13(7q36 1) 173 (20%) 684 0.0177
(1.00) 		0.871
(1.00) 		1
(1.00) 		0.279
(1.00) 		0.303
(1.00) 		0.883
(1.00) 		0.823
(1.00) 		0.907
(1.00)
Del Peak 14(8p23 2) 456 (53%) 401 0.277
(1.00) 		0.679
(1.00) 		0.514
(1.00) 		0.178
(1.00) 		0.654
(1.00) 		0.122
(1.00) 		0.725
(1.00) 		0.985
(1.00)
Del Peak 15(8p11 21) 166 (19%) 691 0.0148
(1.00) 		0.386
(1.00) 		0.219
(1.00) 		0.764
(1.00) 		0.493
(1.00) 		0.0385
(1.00) 		0.216
(1.00) 		0.595
(1.00)
Del Peak 16(9p21 3) 296 (35%) 561 0.0308
(1.00) 		0.686
(1.00) 		0.288
(1.00) 		0.183
(1.00) 		0.165
(1.00) 		0.000587
(0.299) 		0.115
(1.00) 		0.00243
(1.00)
Del Peak 17(9q21 11) 237 (28%) 620 0.508
(1.00) 		0.869
(1.00) 		0.271
(1.00) 		0.86
(1.00) 		0.323
(1.00) 		0.355
(1.00) 		0.62
(1.00) 		0.406
(1.00)
Del Peak 18(10q23 31) 247 (29%) 610 0.875
(1.00) 		0.611
(1.00) 		0.0662
(1.00) 		0.541
(1.00) 		0.823
(1.00) 		0.354
(1.00) 		0.841
(1.00) 		0.598
(1.00)
Del Peak 19(10q26 3) 252 (29%) 605 0.0442
(1.00) 		0.935
(1.00) 		0.296
(1.00) 		0.795
(1.00) 		0.586
(1.00) 		0.272
(1.00) 		0.565
(1.00) 		0.554
(1.00)
Del Peak 20(11p15 5) 250 (29%) 607 0.266
(1.00) 		0.849
(1.00) 		0.295
(1.00) 		0.931
(1.00) 		1
(1.00) 		0.643
(1.00) 		0.106
(1.00) 		0.462
(1.00)
Del Peak 21(11q13 1) 183 (21%) 674 0.36
(1.00) 		0.988
(1.00) 		0.411
(1.00) 		0.563
(1.00) 		0.698
(1.00) 		0.153
(1.00) 		0.592
(1.00) 		0.595
(1.00)
Del Peak 22(11q23 2) 427 (50%) 430 0.356
(1.00) 		0.373
(1.00) 		0.107
(1.00) 		0.937
(1.00) 		0.373
(1.00) 		0.105
(1.00) 		0.491
(1.00) 		0.21
(1.00)
Del Peak 23(11q25) 400 (47%) 457 0.202
(1.00) 		0.0201
(1.00) 		0.0906
(1.00) 		0.527
(1.00) 		0.556
(1.00) 		0.334
(1.00) 		0.532
(1.00) 		0.109
(1.00)
Del Peak 24(12p13 1) 151 (18%) 706 0.578
(1.00) 		0.648
(1.00) 		0.663
(1.00) 		0.407
(1.00) 		0.0509
(1.00) 		0.395
(1.00) 		0.574
(1.00) 		0.216
(1.00)
Del Peak 25(12q24 21) 157 (18%) 700 0.475
(1.00) 		0.227
(1.00) 		1
(1.00) 		0.759
(1.00) 		0.913
(1.00) 		0.192
(1.00) 		0.141
(1.00) 		0.622
(1.00)
Del Peak 26(13q14 2) 396 (46%) 461 0.066
(1.00) 		0.688
(1.00) 		0.74
(1.00) 		0.751
(1.00) 		0.986
(1.00) 		0.477
(1.00) 		0.169
(1.00) 		0.979
(1.00)
Del Peak 27(14q24 3) 276 (32%) 581 0.178
(1.00) 		0.838
(1.00) 		1
(1.00) 		0.446
(1.00) 		0.754
(1.00) 		0.0718
(1.00) 		0.763
(1.00) 		0.851
(1.00)
Del Peak 28(15q13 1) 300 (35%) 557 0.41
(1.00) 		0.252
(1.00) 		1
(1.00) 		0.678
(1.00) 		0.292
(1.00) 		0.16
(1.00) 		0.787
(1.00) 		0.47
(1.00)
Del Peak 29(16q24 3) 553 (65%) 304 0.116
(1.00) 		0.000958
(0.484) 		1
(1.00) 		0.563
(1.00) 		0.182
(1.00) 		0.348
(1.00) 		0.435
(1.00) 		0.253
(1.00)
Del Peak 30(17p12) 519 (61%) 338 0.149
(1.00) 		0.00333
(1.00) 		0.495
(1.00) 		0.627
(1.00) 		0.897
(1.00) 		0.0129
(1.00) 		0.231
(1.00) 		0.609
(1.00)
Del Peak 31(17q21 31) 301 (35%) 556 0.587
(1.00) 		0.000695
(0.353) 		0.172
(1.00) 		0.868
(1.00) 		0.249
(1.00) 		0.0566
(1.00) 		0.114
(1.00) 		0.264
(1.00)
Del Peak 32(18q23) 279 (33%) 578 0.022
(1.00) 		0.525
(1.00) 		1
(1.00) 		0.238
(1.00) 		0.501
(1.00) 		0.0394
(1.00) 		0.165
(1.00) 		0.202
(1.00)
Del Peak 33(19p13 3) 296 (35%) 561 0.41
(1.00) 		0.032
(1.00) 		0.726
(1.00) 		0.74
(1.00) 		0.89
(1.00) 		0.737
(1.00) 		0.2
(1.00) 		0.901
(1.00)
Del Peak 34(19q13 32) 177 (21%) 680 0.854
(1.00) 		0.703
(1.00) 		0.694
(1.00) 		0.696
(1.00) 		0.201
(1.00) 		0.216
(1.00) 		0.931
(1.00) 		0.352
(1.00)
Del Peak 35(20p13) 128 (15%) 729 0.0126
(1.00) 		0.409
(1.00) 		0.63
(1.00) 		0.581
(1.00) 		0.662
(1.00) 		0.969
(1.00) 		0.796
(1.00) 		0.426
(1.00)
Del Peak 36(21q11 2) 176 (21%) 681 0.333
(1.00) 		0.477
(1.00) 		0.217
(1.00) 		0.239
(1.00) 		0.49
(1.00) 		0.231
(1.00) 		0.693
(1.00) 		0.0106
(1.00)
Del Peak 37(22q13 32) 386 (45%) 471 0.495
(1.00) 		0.647
(1.00) 		0.739
(1.00) 		0.0679
(1.00) 		0.743
(1.00) 		0.115
(1.00) 		0.814
(1.00) 		0.874
(1.00)
'Amp Peak 24(17q23.1) mutation analysis' versus 'GENDER'

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

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

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

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

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

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

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

nPatients Mean (Std.Dev)
ALL 856 58.5 (13.2)
DEL PEAK 4(3P14.3) MUTATED 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) mutation analysis' versus Clinical Feature #2: 'AGE'

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

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

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

nPatients Mean (Std.Dev)
ALL 856 58.5 (13.2)
DEL PEAK 11(6Q27) MUTATED 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) mutation analysis' 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)
Copyright © 2013 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle