Glioblastoma Multiforme: 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 57 peak regions and 6 clinical features across 540 patients, 8 significant findings detected with Q value < 0.25.

  • Amp Peak 8(7p11.2) cnvs correlated to 'Time to Death' and 'AGE'.

  • Amp Peak 9(7q21.2) cnvs correlated to 'AGE'.

  • Amp Peak 11(7q32.1) cnvs correlated to 'AGE'.

  • Del Peak 19(10q21.1) cnvs correlated to 'Time to Death' and 'AGE'.

  • Del Peak 20(10q23.31) cnvs correlated to 'Time to Death' and 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 57 regions and 6 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 KARNOFSKY
PERFORMANCE
SCORE 		RADIATIONS
RADIATION
REGIMENINDICATION 		NEOADJUVANT
THERAPY
nCNV (%) nWild-Type logrank test t-test Fisher's exact test t-test Fisher's exact test Fisher's exact test
Amp Peak 8(7p11 2) 458 (85%) 82 0.000367
(0.124) 		3.29e-07
(0.000112) 		0.807
(1.00) 		0.11
(1.00) 		0.124
(1.00) 		0.472
(1.00)
Del Peak 19(10q21 1) 429 (79%) 111 1.82e-06
(0.000615) 		1.79e-10
(6.11e-08) 		0.587
(1.00) 		0.0849
(1.00) 		0.0671
(1.00) 		0.242
(1.00)
Del Peak 20(10q23 31) 451 (84%) 89 0.000503
(0.169) 		2.43e-07
(8.28e-05) 		0.723
(1.00) 		0.0736
(1.00) 		0.804
(1.00) 		0.416
(1.00)
Amp Peak 9(7q21 2) 422 (78%) 118 0.00548
(1.00) 		5.61e-07
(0.00019) 		1
(1.00) 		0.348
(1.00) 		0.221
(1.00) 		0.297
(1.00)
Amp Peak 11(7q32 1) 420 (78%) 120 0.279
(1.00) 		0.000545
(0.183) 		1
(1.00) 		0.727
(1.00) 		0.268
(1.00) 		0.214
(1.00)
Amp Peak 1(1p36 21) 43 (8%) 497 0.28
(1.00) 		0.757
(1.00) 		0.521
(1.00) 		0.527
(1.00) 		0.613
(1.00) 		0.203
(1.00)
Amp Peak 2(1q32 1) 108 (20%) 432 0.934
(1.00) 		0.124
(1.00) 		0.827
(1.00) 		0.278
(1.00) 		0.73
(1.00) 		0.83
(1.00)
Amp Peak 3(1q44) 54 (10%) 486 0.667
(1.00) 		0.809
(1.00) 		0.468
(1.00) 		0.967
(1.00) 		1
(1.00) 		1
(1.00)
Amp Peak 4(2p24 3) 31 (6%) 509 0.146
(1.00) 		0.0658
(1.00) 		0.851
(1.00) 		0.986
(1.00) 		0.0721
(1.00) 		0.46
(1.00)
Amp Peak 5(3q26 33) 70 (13%) 470 0.823
(1.00) 		0.0134
(1.00) 		0.15
(1.00) 		0.575
(1.00) 		1
(1.00) 		0.158
(1.00)
Amp Peak 6(4p16 3) 31 (6%) 509 0.0651
(1.00) 		0.483
(1.00) 		0.573
(1.00) 		0.947
(1.00) 		0.164
(1.00) 		0.198
(1.00)
Amp Peak 7(4q12) 89 (16%) 451 0.913
(1.00) 		0.467
(1.00) 		0.477
(1.00) 		0.918
(1.00) 		0.106
(1.00) 		0.562
(1.00)
Amp Peak 10(7q31 2) 414 (77%) 126 0.0945
(1.00) 		0.00102
(0.342) 		0.917
(1.00) 		0.324
(1.00) 		0.0812
(1.00) 		0.187
(1.00)
Amp Peak 12(8q24 21) 42 (8%) 498 0.249
(1.00) 		0.0571
(1.00) 		0.512
(1.00) 		0.323
(1.00) 		0.731
(1.00) 		0.873
(1.00)
Amp Peak 13(12p13 32) 63 (12%) 477 0.823
(1.00) 		0.068
(1.00) 		0.587
(1.00) 		0.446
(1.00) 		0.314
(1.00) 		0.894
(1.00)
Amp Peak 14(12q14 1) 113 (21%) 427 0.129
(1.00) 		0.559
(1.00) 		0.39
(1.00) 		0.633
(1.00) 		0.91
(1.00) 		1
(1.00)
Amp Peak 15(12q15) 74 (14%) 466 0.553
(1.00) 		0.543
(1.00) 		0.443
(1.00) 		0.743
(1.00) 		0.351
(1.00) 		0.803
(1.00)
Amp Peak 16(13q34) 15 (3%) 525 0.387
(1.00) 		0.895
(1.00) 		0.79
(1.00) 		0.753
(1.00) 		1
(1.00) 		0.611
(1.00)
Amp Peak 17(14q32 33) 16 (3%) 524 0.101
(1.00) 		0.144
(1.00) 		1
(1.00) 		0.222
(1.00) 		1
(1.00) 		1
(1.00)
Del Peak 1(1p36 31) 107 (20%) 433 0.89
(1.00) 		0.0592
(1.00) 		0.0364
(1.00) 		0.645
(1.00) 		1
(1.00) 		0.517
(1.00)
Del Peak 2(1p36 23) 111 (21%) 429 0.788
(1.00) 		0.027
(1.00) 		0.0503
(1.00) 		0.907
(1.00) 		0.253
(1.00) 		0.595
(1.00)
Del Peak 3(1p32 3) 28 (5%) 512 0.8
(1.00) 		0.0764
(1.00) 		0.697
(1.00) 		0.398
(1.00) 		0.098
(1.00) 		0.562
(1.00)
Del Peak 4(1p22 1) 38 (7%) 502 0.241
(1.00) 		0.808
(1.00) 		1
(1.00) 		0.161
(1.00) 		0.857
(1.00) 		1
(1.00)
Del Peak 5(1q42 11) 30 (6%) 510 0.756
(1.00) 		0.571
(1.00) 		0.848
(1.00) 		0.144
(1.00) 		0.551
(1.00) 		0.71
(1.00)
Del Peak 6(1q44) 19 (4%) 521 0.618
(1.00) 		0.668
(1.00) 		0.817
(1.00) 		0.423
(1.00) 		1
(1.00) 		0.484
(1.00)
Del Peak 7(2p25 3) 20 (4%) 520 0.172
(1.00) 		0.321
(1.00) 		0.0664
(1.00) 		0.132
(1.00) 		0.331
(1.00) 		0.823
(1.00)
Del Peak 8(2p14) 22 (4%) 518 0.0141
(1.00) 		0.166
(1.00) 		0.183
(1.00) 		0.721
(1.00) 		0.241
(1.00) 		0.384
(1.00)
Del Peak 9(2q22 1) 15 (3%) 525 0.575
(1.00) 		0.665
(1.00) 		0.295
(1.00) 		0.158
(1.00) 		0.162
(1.00) 		0.611
(1.00)
Del Peak 10(2q37 1) 26 (5%) 514 0.326
(1.00) 		0.0496
(1.00) 		0.153
(1.00) 		0.323
(1.00) 		0.67
(1.00) 		0.689
(1.00)
Del Peak 11(3q13 31) 38 (7%) 502 0.887
(1.00) 		0.178
(1.00) 		0.39
(1.00) 		0.672
(1.00) 		0.588
(1.00) 		0.4
(1.00)
Del Peak 12(3q29) 42 (8%) 498 0.306
(1.00) 		0.216
(1.00) 		0.512
(1.00) 		0.969
(1.00) 		0.492
(1.00) 		0.422
(1.00)
Del Peak 13(4q34 3) 53 (10%) 487 0.174
(1.00) 		0.649
(1.00) 		0.0774
(1.00) 		0.869
(1.00) 		0.162
(1.00) 		0.0842
(1.00)
Del Peak 14(5q13 1) 25 (5%) 515 0.334
(1.00) 		0.575
(1.00) 		0.215
(1.00) 		0.312
(1.00) 		0.827
(1.00) 		1
(1.00)
Del Peak 15(5q34) 27 (5%) 513 0.034
(1.00) 		0.0964
(1.00) 		0.227
(1.00) 		0.532
(1.00) 		0.396
(1.00) 		0.556
(1.00)
Del Peak 16(6q22 31) 105 (19%) 435 0.0408
(1.00) 		0.486
(1.00) 		0.267
(1.00) 		0.824
(1.00) 		0.816
(1.00) 		0.914
(1.00)
Del Peak 17(6q26) 133 (25%) 407 0.292
(1.00) 		0.408
(1.00) 		0.542
(1.00) 		0.825
(1.00) 		0.669
(1.00) 		0.842
(1.00)
Del Peak 18(9p21 3) 391 (72%) 149 0.0431
(1.00) 		0.00134
(0.448) 		0.432
(1.00) 		0.191
(1.00) 		0.68
(1.00) 		0.923
(1.00)
Del Peak 21(11p15 5) 81 (15%) 459 0.0273
(1.00) 		0.00245
(0.813) 		0.539
(1.00) 		0.499
(1.00) 		1
(1.00) 		0.81
(1.00)
Del Peak 22(11p11 2) 63 (12%) 477 0.0861
(1.00) 		0.179
(1.00) 		0.338
(1.00) 		0.908
(1.00) 		0.392
(1.00) 		1
(1.00)
Del Peak 23(12p13 1) 50 (9%) 490 0.303
(1.00) 		0.25
(1.00) 		0.546
(1.00) 		0.13
(1.00) 		0.426
(1.00) 		0.461
(1.00)
Del Peak 24(12q12) 54 (10%) 486 0.713
(1.00) 		0.74
(1.00) 		0.663
(1.00) 		0.841
(1.00) 		0.442
(1.00) 		0.566
(1.00)
Del Peak 25(12q21 31) 40 (7%) 500 0.351
(1.00) 		0.27
(1.00) 		0.317
(1.00) 		0.217
(1.00) 		0.481
(1.00) 		0.744
(1.00)
Del Peak 26(13q14 2) 189 (35%) 351 0.624
(1.00) 		0.637
(1.00) 		0.645
(1.00) 		0.524
(1.00) 		0.498
(1.00) 		0.417
(1.00)
Del Peak 27(13q21 2) 181 (34%) 359 0.821
(1.00) 		0.63
(1.00) 		0.642
(1.00) 		0.717
(1.00) 		1
(1.00) 		0.785
(1.00)
Del Peak 28(14q13 1) 147 (27%) 393 0.842
(1.00) 		0.79
(1.00) 		0.167
(1.00) 		0.468
(1.00) 		0.918
(1.00) 		0.333
(1.00)
Del Peak 29(15q14) 103 (19%) 437 0.399
(1.00) 		0.232
(1.00) 		0.576
(1.00) 		0.976
(1.00) 		0.907
(1.00) 		0.743
(1.00)
Del Peak 30(15q21 1) 92 (17%) 448 0.272
(1.00) 		0.104
(1.00) 		0.907
(1.00) 		0.691
(1.00) 		0.902
(1.00) 		0.569
(1.00)
Del Peak 31(16p12 2) 53 (10%) 487 0.18
(1.00) 		0.11
(1.00) 		0.38
(1.00) 		0.566
(1.00) 		0.278
(1.00) 		0.39
(1.00)
Del Peak 32(16q12 1) 54 (10%) 486 0.00264
(0.873) 		0.851
(1.00) 		0.77
(1.00) 		0.157
(1.00) 		0.878
(1.00) 		0.25
(1.00)
Del Peak 33(16q23 1) 55 (10%) 485 0.0179
(1.00) 		0.311
(1.00) 		0.563
(1.00) 		0.0493
(1.00) 		0.289
(1.00) 		0.199
(1.00)
Del Peak 34(17p13 1) 64 (12%) 476 0.418
(1.00) 		0.0179
(1.00) 		0.0562
(1.00) 		0.778
(1.00) 		0.669
(1.00) 		0.287
(1.00)
Del Peak 35(17q11 2) 38 (7%) 502 0.42
(1.00) 		0.26
(1.00) 		0.497
(1.00) 		0.263
(1.00) 		1
(1.00) 		0.4
(1.00)
Del Peak 36(18q22 3) 54 (10%) 486 0.632
(1.00) 		0.358
(1.00) 		0.468
(1.00) 		0.025
(1.00) 		1
(1.00) 		0.319
(1.00)
Del Peak 37(19q13 41) 71 (13%) 469 0.0201
(1.00) 		0.397
(1.00) 		0.897
(1.00) 		0.369
(1.00) 		0.412
(1.00) 		0.61
(1.00)
Del Peak 38(19q13 43) 61 (11%) 479 0.0398
(1.00) 		0.0363
(1.00) 		0.58
(1.00) 		0.829
(1.00) 		0.243
(1.00) 		0.892
(1.00)
Del Peak 39(21q21 1) 39 (7%) 501 0.976
(1.00) 		0.362
(1.00) 		0.402
(1.00) 		0.674
(1.00) 		0.594
(1.00) 		0.621
(1.00)
Del Peak 40(22q13 32) 164 (30%) 376 0.859
(1.00) 		0.0163
(1.00) 		0.294
(1.00) 		0.555
(1.00) 		0.763
(1.00) 		1
(1.00)
'Amp Peak 8(7p11.2) mutation analysis' versus 'Time to Death'

P value = 0.000367 (logrank test), Q value = 0.12

Table S1.  Gene #8: 'Amp Peak 8(7p11.2) mutation analysis' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 540 407 0.1 - 127.6 (9.6)
AMP PEAK 8(7P11.2) MUTATED 458 347 0.1 - 127.6 (9.2)
AMP PEAK 8(7P11.2) WILD-TYPE 82 60 0.2 - 108.8 (12.7)

Figure S1.  Get High-res Image Gene #8: 'Amp Peak 8(7p11.2) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Amp Peak 8(7p11.2) mutation analysis' versus 'AGE'

P value = 3.29e-07 (t-test), Q value = 0.00011

Table S2.  Gene #8: 'Amp Peak 8(7p11.2) mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 540 57.8 (14.3)
AMP PEAK 8(7P11.2) MUTATED 458 59.6 (12.5)
AMP PEAK 8(7P11.2) WILD-TYPE 82 47.5 (19.1)

Figure S2.  Get High-res Image Gene #8: 'Amp Peak 8(7p11.2) mutation analysis' versus Clinical Feature #2: 'AGE'

'Amp Peak 9(7q21.2) mutation analysis' versus 'AGE'

P value = 5.61e-07 (t-test), Q value = 0.00019

Table S3.  Gene #9: 'Amp Peak 9(7q21.2) mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 540 57.8 (14.3)
AMP PEAK 9(7Q21.2) MUTATED 422 59.8 (12.1)
AMP PEAK 9(7Q21.2) WILD-TYPE 118 50.4 (18.6)

Figure S3.  Get High-res Image Gene #9: 'Amp Peak 9(7q21.2) mutation analysis' versus Clinical Feature #2: 'AGE'

'Amp Peak 11(7q32.1) mutation analysis' versus 'AGE'

P value = 0.000545 (t-test), Q value = 0.18

Table S4.  Gene #11: 'Amp Peak 11(7q32.1) mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 540 57.8 (14.3)
AMP PEAK 11(7Q32.1) MUTATED 420 59.2 (12.7)
AMP PEAK 11(7Q32.1) WILD-TYPE 120 52.9 (18.2)

Figure S4.  Get High-res Image Gene #11: 'Amp Peak 11(7q32.1) mutation analysis' versus Clinical Feature #2: 'AGE'

'Del Peak 19(10q21.1) mutation analysis' versus 'Time to Death'

P value = 1.82e-06 (logrank test), Q value = 0.00062

Table S5.  Gene #36: 'Del Peak 19(10q21.1) mutation analysis' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 540 407 0.1 - 127.6 (9.6)
DEL PEAK 19(10Q21.1) MUTATED 429 328 0.1 - 77.6 (9.3)
DEL PEAK 19(10Q21.1) WILD-TYPE 111 79 0.2 - 127.6 (10.8)

Figure S5.  Get High-res Image Gene #36: 'Del Peak 19(10q21.1) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 19(10q21.1) mutation analysis' versus 'AGE'

P value = 1.79e-10 (t-test), Q value = 6.1e-08

Table S6.  Gene #36: 'Del Peak 19(10q21.1) mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 540 57.8 (14.3)
DEL PEAK 19(10Q21.1) MUTATED 429 60.3 (12.0)
DEL PEAK 19(10Q21.1) WILD-TYPE 111 47.9 (17.9)

Figure S6.  Get High-res Image Gene #36: 'Del Peak 19(10q21.1) mutation analysis' versus Clinical Feature #2: 'AGE'

'Del Peak 20(10q23.31) mutation analysis' versus 'Time to Death'

P value = 0.000503 (logrank test), Q value = 0.17

Table S7.  Gene #37: 'Del Peak 20(10q23.31) mutation analysis' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 540 407 0.1 - 127.6 (9.6)
DEL PEAK 20(10Q23.31) MUTATED 451 344 0.1 - 127.6 (9.5)
DEL PEAK 20(10Q23.31) WILD-TYPE 89 63 0.2 - 108.8 (10.3)

Figure S7.  Get High-res Image Gene #37: 'Del Peak 20(10q23.31) mutation analysis' versus Clinical Feature #1: 'Time to Death'

'Del Peak 20(10q23.31) mutation analysis' versus 'AGE'

P value = 2.43e-07 (t-test), Q value = 8.3e-05

Table S8.  Gene #37: 'Del Peak 20(10q23.31) mutation analysis' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 540 57.8 (14.3)
DEL PEAK 20(10Q23.31) MUTATED 451 59.6 (12.7)
DEL PEAK 20(10Q23.31) WILD-TYPE 89 48.5 (18.1)

Figure S8.  Get High-res Image Gene #37: 'Del Peak 20(10q23.31) mutation analysis' versus Clinical Feature #2: 'AGE'

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 = GBM.clin.merged.picked.txt

  • Number of patients = 540

  • Number of copy number variation regions = 57

  • Number of selected clinical features = 6

  • 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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