Breast Invasive Carcinoma: Correlation between copy number variation genes 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 copy number variation (cnv) genes and selected clinical features.

Summary

Testing the association between copy number variation of 68 peak regions and 5 clinical features across 843 patients, 5 significant findings detected with Q value < 0.25.

  • Amp Peak 25(17q23.1) cnvs correlated to 'GENDER'.

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

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

  • Del Peak 16(9p23) cnvs correlated to 'Time to Death'.

  • Del Peak 17(9p21.3) cnvs correlated to 'NEOADJUVANT.THERAPY'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 68 regions and 5 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 		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
Amp Peak 25(17q23 1) 351 (42%) 492 0.0679
(1.00) 		0.877
(1.00) 		0.000354
(0.119) 		0.458
(1.00) 		0.0196
(1.00)
Del Peak 4(3p14 3) 266 (32%) 577 0.0195
(1.00) 		9.87e-05
(0.0336) 		1
(1.00) 		0.54
(1.00) 		0.938
(1.00)
Del Peak 11(6q27) 289 (34%) 554 0.132
(1.00) 		0.000126
(0.0427) 		0.176
(1.00) 		0.347
(1.00) 		1
(1.00)
Del Peak 16(9p23) 261 (31%) 582 0.000703
(0.236) 		0.401
(1.00) 		0.47
(1.00) 		0.134
(1.00) 		0.00509
(1.00)
Del Peak 17(9p21 3) 293 (35%) 550 0.0322
(1.00) 		0.599
(1.00) 		0.289
(1.00) 		0.124
(1.00) 		0.000212
(0.0715)
Amp Peak 1(1p22 3) 186 (22%) 657 0.981
(1.00) 		0.837
(1.00) 		1
(1.00) 		0.493
(1.00) 		0.545
(1.00)
Amp Peak 2(1q21 3) 605 (72%) 238 0.808
(1.00) 		0.513
(1.00) 		0.28
(1.00) 		0.176
(1.00) 		1
(1.00)
Amp Peak 3(1q44) 605 (72%) 238 0.0119
(1.00) 		0.868
(1.00) 		0.718
(1.00) 		0.418
(1.00) 		0.75
(1.00)
Amp Peak 4(3p26 1) 178 (21%) 665 0.00479
(1.00) 		0.498
(1.00) 		0.217
(1.00) 		0.62
(1.00) 		0.481
(1.00)
Amp Peak 5(3q26 32) 276 (33%) 567 0.629
(1.00) 		0.307
(1.00) 		0.726
(1.00) 		0.0826
(1.00) 		0.401
(1.00)
Amp Peak 6(4q13 3) 138 (16%) 705 0.00224
(0.745) 		0.384
(1.00) 		1
(1.00) 		0.912
(1.00) 		0.561
(1.00)
Amp Peak 7(6p23) 222 (26%) 621 0.633
(1.00) 		0.377
(1.00) 		0.458
(1.00) 		0.268
(1.00) 		0.625
(1.00)
Amp Peak 8(6q21) 156 (19%) 687 0.0119
(1.00) 		0.6
(1.00) 		1
(1.00) 		0.464
(1.00) 		0.711
(1.00)
Amp Peak 9(8p11 23) 324 (38%) 519 0.0278
(1.00) 		0.0869
(1.00) 		0.165
(1.00) 		0.738
(1.00) 		1
(1.00)
Amp Peak 10(8p11 21) 329 (39%) 514 0.84
(1.00) 		0.0393
(1.00) 		0.0987
(1.00) 		0.0197
(1.00) 		0.607
(1.00)
Amp Peak 11(8q24 21) 550 (65%) 293 0.119
(1.00) 		0.149
(1.00) 		0.727
(1.00) 		0.393
(1.00) 		0.763
(1.00)
Amp Peak 12(10p15 1) 242 (29%) 601 0.204
(1.00) 		0.649
(1.00) 		0.0665
(1.00) 		0.208
(1.00) 		0.751
(1.00)
Amp Peak 13(10q22 3) 127 (15%) 716 0.116
(1.00) 		0.944
(1.00) 		1
(1.00) 		0.649
(1.00) 		0.616
(1.00)
Amp Peak 14(11p13) 180 (21%) 663 0.462
(1.00) 		0.795
(1.00) 		1
(1.00) 		0.323
(1.00) 		0.793
(1.00)
Amp Peak 15(11q13 3) 327 (39%) 516 0.24
(1.00) 		0.285
(1.00) 		0.32
(1.00) 		0.677
(1.00) 		0.21
(1.00)
Amp Peak 16(11q14 1) 211 (25%) 632 0.0932
(1.00) 		0.333
(1.00) 		0.698
(1.00) 		0.574
(1.00) 		0.0308
(1.00)
Amp Peak 17(12p13 33) 220 (26%) 623 0.802
(1.00) 		0.631
(1.00) 		0.459
(1.00) 		0.0521
(1.00) 		0.807
(1.00)
Amp Peak 18(12q15) 223 (26%) 620 0.0389
(1.00) 		0.25
(1.00) 		0.0129
(1.00) 		1
(1.00) 		0.0875
(1.00)
Amp Peak 19(13q12 3) 124 (15%) 719 0.0366
(1.00) 		0.281
(1.00) 		0.628
(1.00) 		0.252
(1.00) 		0.612
(1.00)
Amp Peak 20(13q34) 146 (17%) 697 0.977
(1.00) 		0.119
(1.00) 		0.372
(1.00) 		0.669
(1.00) 		0.57
(1.00)
Amp Peak 21(14q21 1) 175 (21%) 668 0.428
(1.00) 		0.0408
(1.00) 		0.694
(1.00) 		0.92
(1.00) 		0.215
(1.00)
Amp Peak 22(15q26 3) 156 (19%) 687 0.214
(1.00) 		0.0408
(1.00) 		0.0661
(1.00) 		0.834
(1.00) 		0.644
(1.00)
Amp Peak 23(17p11 2) 118 (14%) 725 0.133
(1.00) 		0.134
(1.00) 		0.119
(1.00) 		0.0999
(1.00) 		0.68
(1.00)
Amp Peak 24(17q12) 277 (33%) 566 0.175
(1.00) 		0.653
(1.00) 		0.000815
(0.273) 		0.931
(1.00) 		0.193
(1.00)
Amp Peak 26(19q12) 217 (26%) 626 0.401
(1.00) 		0.47
(1.00) 		0.702
(1.00) 		0.136
(1.00) 		1
(1.00)
Amp Peak 27(19q13 42) 226 (27%) 617 0.644
(1.00) 		0.268
(1.00) 		0.259
(1.00) 		0.359
(1.00) 		0.746
(1.00)
Amp Peak 28(20q13 2) 439 (52%) 404 0.689
(1.00) 		0.333
(1.00) 		0.181
(1.00) 		0.073
(1.00) 		0.565
(1.00)
Del Peak 1(1p36 13) 357 (42%) 486 0.207
(1.00) 		0.372
(1.00) 		0.179
(1.00) 		0.742
(1.00) 		0.19
(1.00)
Del Peak 2(1p21 2) 288 (34%) 555 0.0626
(1.00) 		0.113
(1.00) 		1
(1.00) 		0.23
(1.00) 		0.00793
(1.00)
Del Peak 3(2q37 3) 250 (30%) 593 0.886
(1.00) 		0.958
(1.00) 		0.294
(1.00) 		0.657
(1.00) 		1
(1.00)
Del Peak 5(4p16 3) 265 (31%) 578 0.833
(1.00) 		0.0953
(1.00) 		0.727
(1.00) 		0.6
(1.00) 		0.487
(1.00)
Del Peak 6(4q35 2) 265 (31%) 578 0.112
(1.00) 		0.673
(1.00) 		0.286
(1.00) 		0.93
(1.00) 		0.246
(1.00)
Del Peak 7(5q11 2) 220 (26%) 623 0.232
(1.00) 		0.00997
(1.00) 		0.459
(1.00) 		0.579
(1.00) 		0.0603
(1.00)
Del Peak 8(5q21 3) 212 (25%) 631 0.349
(1.00) 		0.0174
(1.00) 		0.122
(1.00) 		0.779
(1.00) 		0.0821
(1.00)
Del Peak 9(6p25 3) 159 (19%) 684 0.566
(1.00) 		0.0626
(1.00) 		0.681
(1.00) 		0.252
(1.00) 		0.713
(1.00)
Del Peak 10(6q15) 284 (34%) 559 0.405
(1.00) 		0.106
(1.00) 		0.725
(1.00) 		0.606
(1.00) 		0.224
(1.00)
Del Peak 12(7p22 3) 114 (14%) 729 0.107
(1.00) 		0.34
(1.00) 		0.618
(1.00) 		0.554
(1.00) 		1
(1.00)
Del Peak 13(7q36 1) 171 (20%) 672 0.0181
(1.00) 		0.863
(1.00) 		1
(1.00) 		0.266
(1.00) 		0.212
(1.00)
Del Peak 14(8p23 2) 448 (53%) 395 0.276
(1.00) 		0.702
(1.00) 		0.513
(1.00) 		0.222
(1.00) 		0.349
(1.00)
Del Peak 15(8p11 21) 162 (19%) 681 0.0142
(1.00) 		0.315
(1.00) 		0.22
(1.00) 		0.606
(1.00) 		0.649
(1.00)
Del Peak 18(9q21 11) 232 (28%) 611 0.506
(1.00) 		0.924
(1.00) 		0.269
(1.00) 		0.927
(1.00) 		0.00783
(1.00)
Del Peak 19(9q34 3) 221 (26%) 622 0.961
(1.00) 		0.49
(1.00) 		0.058
(1.00) 		0.927
(1.00) 		0.0409
(1.00)
Del Peak 20(10q23 31) 244 (29%) 599 0.868
(1.00) 		0.621
(1.00) 		0.0659
(1.00) 		0.474
(1.00) 		0.268
(1.00)
Del Peak 21(10q26 3) 246 (29%) 597 0.0426
(1.00) 		0.788
(1.00) 		0.46
(1.00) 		0.789
(1.00) 		0.385
(1.00)
Del Peak 22(11p15 5) 248 (29%) 595 0.271
(1.00) 		0.845
(1.00) 		0.461
(1.00) 		0.929
(1.00) 		0.387
(1.00)
Del Peak 23(11q13 1) 182 (22%) 661 0.365
(1.00) 		0.927
(1.00) 		0.415
(1.00) 		0.429
(1.00) 		0.432
(1.00)
Del Peak 24(11q23 2) 421 (50%) 422 0.364
(1.00) 		0.386
(1.00) 		0.107
(1.00) 		0.745
(1.00) 		0.774
(1.00)
Del Peak 25(11q25) 394 (47%) 449 0.205
(1.00) 		0.0232
(1.00) 		0.0908
(1.00) 		0.683
(1.00) 		0.885
(1.00)
Del Peak 26(12p13 1) 151 (18%) 692 0.573
(1.00) 		0.626
(1.00) 		0.667
(1.00) 		0.525
(1.00) 		0.303
(1.00)
Del Peak 27(12q23 1) 146 (17%) 697 0.991
(1.00) 		0.476
(1.00) 		1
(1.00) 		1
(1.00) 		0.256
(1.00)
Del Peak 28(12q24 31) 147 (17%) 696 0.243
(1.00) 		0.374
(1.00) 		0.372
(1.00) 		0.592
(1.00) 		0.449
(1.00)
Del Peak 29(13q14 2) 390 (46%) 453 0.0661
(1.00) 		0.808
(1.00) 		0.74
(1.00) 		0.683
(1.00) 		0.773
(1.00)
Del Peak 30(14q24 3) 270 (32%) 573 0.175
(1.00) 		0.928
(1.00) 		1
(1.00) 		0.794
(1.00) 		0.355
(1.00)
Del Peak 31(15q13 1) 296 (35%) 547 0.413
(1.00) 		0.234
(1.00) 		1
(1.00) 		0.551
(1.00) 		0.499
(1.00)
Del Peak 32(16q24 3) 545 (65%) 298 0.115
(1.00) 		0.000898
(0.3) 		1
(1.00) 		0.61
(1.00) 		0.652
(1.00)
Del Peak 33(17p12) 511 (61%) 332 0.148
(1.00) 		0.00349
(1.00) 		0.495
(1.00) 		0.868
(1.00) 		0.556
(1.00)
Del Peak 34(17q12) 285 (34%) 558 0.668
(1.00) 		0.00354
(1.00) 		0.726
(1.00) 		0.198
(1.00) 		0.197
(1.00)
Del Peak 35(18q23) 278 (33%) 565 0.0228
(1.00) 		0.569
(1.00) 		1
(1.00) 		0.167
(1.00) 		0.879
(1.00)
Del Peak 36(19p13 3) 293 (35%) 550 0.415
(1.00) 		0.0351
(1.00) 		0.727
(1.00) 		0.733
(1.00) 		0.0287
(1.00)
Del Peak 37(19q13 32) 174 (21%) 669 0.875
(1.00) 		0.742
(1.00) 		0.694
(1.00) 		0.841
(1.00) 		0.215
(1.00)
Del Peak 38(20p13) 125 (15%) 718 0.0126
(1.00) 		0.517
(1.00) 		0.629
(1.00) 		0.362
(1.00) 		0.0337
(1.00)
Del Peak 39(21q11 2) 175 (21%) 668 0.338
(1.00) 		0.488
(1.00) 		0.217
(1.00) 		0.367
(1.00) 		0.0102
(1.00)
Del Peak 40(22q13 32) 379 (45%) 464 0.492
(1.00) 		0.603
(1.00) 		0.739
(1.00) 		0.0718
(1.00) 		0.829
(1.00)
'Amp Peak 25(17q23.1) mutation analysis' versus 'GENDER'

P value = 0.000354 (Fisher's exact test), Q value = 0.12

Table S1.  Gene #25: 'Amp Peak 25(17q23.1) mutation analysis' versus Clinical Feature #3: 'GENDER'

nPatients FEMALE MALE
ALL 834 9
AMP PEAK 25(17Q23.1) MUTATED 342 9
AMP PEAK 25(17Q23.1) WILD-TYPE 492 0

Figure S1.  Get High-res Image Gene #25: 'Amp Peak 25(17q23.1) mutation analysis' versus Clinical Feature #3: 'GENDER'

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

P value = 9.87e-05 (t-test), Q value = 0.034

Table S2.  Gene #32: 'Del Peak 4(3p14.3) mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 842 58.5 (13.2)
DEL PEAK 4(3P14.3) MUTATED 266 55.9 (13.2)
DEL PEAK 4(3P14.3) WILD-TYPE 576 59.7 (13.1)

Figure S2.  Get High-res Image Gene #32: 'Del Peak 4(3p14.3) mutation analysis' versus Clinical Feature #2: 'AGE'

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

P value = 0.000126 (t-test), Q value = 0.043

Table S3.  Gene #39: 'Del Peak 11(6q27) mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 842 58.5 (13.2)
DEL PEAK 11(6Q27) MUTATED 289 56.1 (12.8)
DEL PEAK 11(6Q27) WILD-TYPE 553 59.8 (13.3)

Figure S3.  Get High-res Image Gene #39: 'Del Peak 11(6q27) mutation analysis' versus Clinical Feature #2: 'AGE'

'Del Peak 16(9p23) mutation analysis' versus 'Time to Death'

P value = 0.000703 (logrank test), Q value = 0.24

Table S4.  Gene #44: 'Del Peak 16(9p23) mutation analysis' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 785 94 0.0 - 223.4 (18.4)
DEL PEAK 16(9P23) MUTATED 240 34 0.1 - 162.0 (17.0)
DEL PEAK 16(9P23) WILD-TYPE 545 60 0.0 - 223.4 (19.2)

Figure S4.  Get High-res Image Gene #44: 'Del Peak 16(9p23) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 17(9p21.3) mutation analysis' versus 'NEOADJUVANT.THERAPY'

P value = 0.000212 (Fisher's exact test), Q value = 0.072

Table S5.  Gene #45: 'Del Peak 17(9p21.3) mutation analysis' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

nPatients NO YES
ALL 542 301
DEL PEAK 17(9P21.3) MUTATED 213 80
DEL PEAK 17(9P21.3) WILD-TYPE 329 221

Figure S5.  Get High-res Image Gene #45: 'Del Peak 17(9p21.3) mutation analysis' versus Clinical Feature #5: 'NEOADJUVANT.THERAPY'

Methods & Data
Input

  • Copy number data file = All Lesions File (all_lesions.conf_##.txt, where ## is the confidence level). The all lesions file is from GISTIC pipeline and summarizes the results from the GISTIC run. It contains data about the significant regions of amplification and deletion as well as which samples are amplified or deleted in each of these regions. The identified regions are listed down the first column, and the samples are listed across the first row, starting in column 10.

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

  • Number of patients = 843

  • Number of copy number variation regions = 68

  • Number of selected clinical features = 5

  • Exclude regions that fewer than K tumors have alterations, K = 3

Survival analysis

For survival clinical features, the Kaplan-Meier survival curves of tumors with and without gene cnvs 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 cnvs 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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