Correlation between copy number variations of arm-level result and selected clinical features
Brain Lower Grade Glioma (Primary solid tumor)
23 May 2013  |  analyses__2013_05_23
Maintainer Information
Citation Information
doi:10.7908/C1JH3J73
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between copy number variations of arm-level result and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1JH3J73
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 50 arm-level results and 6 clinical features across 207 patients, 17 significant findings detected with Q value < 0.25.

  • 12q gain cnv correlated to 'AGE'.

  • 19q gain cnv correlated to 'Time to Death'.

  • 20p gain cnv correlated to 'Time to Death'.

  • 20q gain cnv correlated to 'Time to Death'.

  • 1p loss cnv correlated to 'HISTOLOGICAL.TYPE'.

  • 3p loss cnv correlated to 'AGE'.

  • 6p loss cnv correlated to 'Time to Death'.

  • 10p loss cnv correlated to 'Time to Death',  'AGE', and 'HISTOLOGICAL.TYPE'.

  • 10q loss cnv correlated to 'Time to Death',  'AGE', and 'HISTOLOGICAL.TYPE'.

  • 11q loss cnv correlated to 'Time to Death'.

  • 14q loss cnv correlated to 'Time to Death'.

  • 19q loss cnv correlated to 'HISTOLOGICAL.TYPE'.

  • 22q loss cnv correlated to 'Time to Death'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 50 arm-level results and 6 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 17 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER KARNOFSKY
PERFORMANCE
SCORE 		HISTOLOGICAL
TYPE 		RADIATIONS
RADIATION
REGIMENINDICATION
nCNV (%) nWild-Type logrank test t-test Fisher's exact test t-test Fisher's exact test Fisher's exact test
10p loss 0 (0%) 177 8.93e-11
(2.55e-08) 		6.05e-08
(1.71e-05) 		0.0478
(1.00) 		0.879
(1.00) 		0.00083
(0.227) 		0.319
(1.00)
10q loss 0 (0%) 176 1.88e-10
(5.35e-08) 		3.06e-08
(8.68e-06) 		0.0308
(1.00) 		0.927
(1.00) 		0.000389
(0.108) 		0.549
(1.00)
12q gain 0 (0%) 203 0.364
(1.00) 		0.000869
(0.236) 		0.136
(1.00) 		1
(1.00) 		1
(1.00)
19q gain 0 (0%) 199 0.000661
(0.182) 		0.0102
(1.00) 		1
(1.00) 		0.26
(1.00) 		0.595
(1.00) 		0.265
(1.00)
20p gain 0 (0%) 190 0.000116
(0.0324) 		0.00665
(1.00) 		0.0744
(1.00) 		0.976
(1.00) 		0.175
(1.00) 		0.604
(1.00)
20q gain 0 (0%) 192 0.000335
(0.0933) 		0.0141
(1.00) 		0.0627
(1.00) 		0.893
(1.00) 		0.16
(1.00) 		0.787
(1.00)
1p loss 0 (0%) 142 0.124
(1.00) 		0.0169
(1.00) 		0.88
(1.00) 		0.692
(1.00) 		4.61e-19
(1.33e-16) 		0.0663
(1.00)
3p loss 0 (0%) 203 0.917
(1.00) 		1.04e-05
(0.00291) 		0.636
(1.00) 		0.688
(1.00) 		0.301
(1.00)
6p loss 0 (0%) 202 5.29e-05
(0.0148) 		0.806
(1.00) 		1
(1.00) 		0.861
(1.00) 		0.449
(1.00) 		0.651
(1.00)
11q loss 0 (0%) 203 0.000569
(0.157) 		0.0656
(1.00) 		0.316
(1.00) 		0.214
(1.00) 		1
(1.00)
14q loss 0 (0%) 185 0.000835
(0.228) 		0.0113
(1.00) 		0.0432
(1.00) 		0.5
(1.00) 		0.0839
(1.00) 		0.163
(1.00)
19q loss 0 (0%) 134 0.186
(1.00) 		0.0459
(1.00) 		0.769
(1.00) 		0.825
(1.00) 		2.67e-14
(7.66e-12) 		0.372
(1.00)
22q loss 0 (0%) 193 3.89e-06
(0.0011) 		0.452
(1.00) 		0.28
(1.00) 		0.187
(1.00) 		0.00293
(0.774) 		1
(1.00)
1p gain 0 (0%) 201 0.00425
(1.00) 		0.171
(1.00) 		0.0864
(1.00) 		0.14
(1.00) 		0.0282
(1.00) 		1
(1.00)
1q gain 0 (0%) 199 0.252
(1.00) 		0.00496
(1.00) 		0.293
(1.00) 		0.572
(1.00) 		0.432
(1.00) 		1
(1.00)
6p gain 0 (0%) 204 0.506
(1.00) 		0.761
(1.00) 		0.578
(1.00) 		0.0449
(1.00) 		0.0564
(1.00)
7p gain 0 (0%) 171 0.00841
(1.00) 		0.0264
(1.00) 		0.044
(1.00) 		0.958
(1.00) 		0.0204
(1.00) 		0.851
(1.00)
7q gain 0 (0%) 158 0.0113
(1.00) 		0.00174
(0.467) 		0.137
(1.00) 		0.702
(1.00) 		0.0623
(1.00) 		1
(1.00)
8p gain 0 (0%) 193 0.731
(1.00) 		0.618
(1.00) 		0.403
(1.00) 		0.987
(1.00) 		0.159
(1.00) 		0.78
(1.00)
8q gain 0 (0%) 190 0.941
(1.00) 		0.271
(1.00) 		0.613
(1.00) 		0.348
(1.00) 		0.0511
(1.00) 		0.801
(1.00)
9p gain 0 (0%) 203 0.135
(1.00) 		0.00595
(1.00) 		0.316
(1.00) 		0.817
(1.00) 		1
(1.00)
9q gain 0 (0%) 203 0.043
(1.00) 		0.0912
(1.00) 		0.316
(1.00) 		0.14
(1.00) 		0.214
(1.00) 		0.641
(1.00)
10p gain 0 (0%) 186 0.502
(1.00) 		0.00632
(1.00) 		0.0669
(1.00) 		0.101
(1.00) 		0.101
(1.00) 		0.00172
(0.465)
11p gain 0 (0%) 198 0.511
(1.00) 		0.277
(1.00) 		1
(1.00) 		0.722
(1.00) 		0.469
(1.00) 		1
(1.00)
11q gain 0 (0%) 194 0.69
(1.00) 		0.185
(1.00) 		0.564
(1.00) 		0.605
(1.00) 		0.875
(1.00) 		0.77
(1.00)
12p gain 0 (0%) 197 0.465
(1.00) 		0.00184
(0.493) 		0.0458
(1.00) 		0.758
(1.00) 		1
(1.00)
18p gain 0 (0%) 203 0.493
(1.00) 		0.75
(1.00) 		0.316
(1.00) 		0.214
(1.00) 		1
(1.00)
19p gain 0 (0%) 197 0.171
(1.00) 		0.00203
(0.542) 		1
(1.00) 		0.0572
(1.00) 		0.293
(1.00) 		0.19
(1.00)
21q gain 0 (0%) 204 0.533
(1.00) 		0.994
(1.00) 		1
(1.00) 		0.26
(1.00) 		1
(1.00)
1q loss 0 (0%) 198 0.489
(1.00) 		0.047
(1.00) 		1
(1.00) 		0.111
(1.00) 		0.00112
(0.303) 		0.487
(1.00)
2p loss 0 (0%) 203 0.054
(1.00) 		0.675
(1.00) 		0.636
(1.00) 		0.688
(1.00) 		0.641
(1.00)
2q loss 0 (0%) 204 0.539
(1.00) 		0.189
(1.00) 		0.261
(1.00) 		0.108
(1.00) 		0.561
(1.00)
3q loss 0 (0%) 198 0.554
(1.00) 		0.857
(1.00) 		0.735
(1.00) 		0.217
(1.00) 		0.387
(1.00) 		0.312
(1.00)
4p loss 0 (0%) 192 0.143
(1.00) 		0.252
(1.00) 		0.279
(1.00) 		0.563
(1.00) 		0.0664
(1.00) 		0.585
(1.00)
4q loss 0 (0%) 183 0.116
(1.00) 		0.88
(1.00) 		0.663
(1.00) 		0.395
(1.00) 		0.314
(1.00) 		0.659
(1.00)
5p loss 0 (0%) 196 0.309
(1.00) 		0.814
(1.00) 		0.358
(1.00) 		0.212
(1.00) 		0.00272
(0.722) 		0.343
(1.00)
5q loss 0 (0%) 198 0.0292
(1.00) 		0.364
(1.00) 		1
(1.00) 		0.14
(1.00) 		0.224
(1.00) 		0.0913
(1.00)
6q loss 0 (0%) 188 0.00251
(0.666) 		0.134
(1.00) 		0.467
(1.00) 		0.194
(1.00) 		0.025
(1.00) 		0.22
(1.00)
9p loss 0 (0%) 171 0.00408
(1.00) 		0.126
(1.00) 		0.855
(1.00) 		0.595
(1.00) 		0.0808
(1.00) 		0.025
(1.00)
9q loss 0 (0%) 201 0.851
(1.00) 		0.116
(1.00) 		0.406
(1.00) 		0.615
(1.00) 		0.579
(1.00) 		1
(1.00)
11p loss 0 (0%) 189 0.131
(1.00) 		0.111
(1.00) 		0.621
(1.00) 		0.797
(1.00) 		0.00472
(1.00) 		0.0464
(1.00)
12q loss 0 (0%) 199 0.464
(1.00) 		0.894
(1.00) 		0.727
(1.00) 		0.859
(1.00) 		0.214
(1.00) 		0.0573
(1.00)
13q loss 0 (0%) 180 0.163
(1.00) 		0.397
(1.00) 		1
(1.00) 		0.839
(1.00) 		1
(1.00) 		0.0593
(1.00)
15q loss 0 (0%) 195 0.252
(1.00) 		0.734
(1.00) 		0.561
(1.00) 		0.816
(1.00) 		0.0384
(1.00) 		0.377
(1.00)
16q loss 0 (0%) 201 0.962
(1.00) 		0.178
(1.00) 		1
(1.00) 		0.879
(1.00) 		0.678
(1.00)
18p loss 0 (0%) 193 0.69
(1.00) 		0.409
(1.00) 		1
(1.00) 		0.5
(1.00) 		0.606
(1.00) 		1
(1.00)
18q loss 0 (0%) 192 0.813
(1.00) 		0.367
(1.00) 		0.428
(1.00) 		0.731
(1.00) 		0.182
(1.00) 		0.787
(1.00)
19p loss 0 (0%) 198 0.484
(1.00) 		0.247
(1.00) 		0.503
(1.00) 		0.44
(1.00) 		0.198
(1.00) 		0.737
(1.00)
21q loss 0 (0%) 200 0.431
(1.00) 		0.746
(1.00) 		1
(1.00) 		0.26
(1.00) 		0.0666
(1.00) 		0.253
(1.00)
Xq loss 0 (0%) 202 0.423
(1.00) 		0.794
(1.00) 		0.654
(1.00) 		0.578
(1.00) 		0.377
(1.00)
'12q gain' versus 'AGE'

P value = 0.000869 (t-test), Q value = 0.24

Table S1.  Gene #14: '12q gain' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 207 43.1 (13.4)
12Q GAIN CNV 4 29.2 (3.5)
12Q GAIN WILD-TYPE 203 43.4 (13.4)

Figure S1.  Get High-res Image Gene #14: '12q gain' versus Clinical Feature #2: 'AGE'

'19q gain' versus 'Time to Death'

P value = 0.000661 (logrank test), Q value = 0.18

Table S2.  Gene #17: '19q gain' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
19Q GAIN CNV 8 4 0.5 - 26.3 (14.5)
19Q GAIN WILD-TYPE 198 47 0.0 - 211.2 (13.4)

Figure S2.  Get High-res Image Gene #17: '19q gain' versus Clinical Feature #1: 'Time to Death'

'20p gain' versus 'Time to Death'

P value = 0.000116 (logrank test), Q value = 0.032

Table S3.  Gene #18: '20p gain' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
20P GAIN CNV 17 7 0.5 - 41.1 (15.3)
20P GAIN WILD-TYPE 189 44 0.0 - 211.2 (13.4)

Figure S3.  Get High-res Image Gene #18: '20p gain' versus Clinical Feature #1: 'Time to Death'

'20q gain' versus 'Time to Death'

P value = 0.000335 (logrank test), Q value = 0.093

Table S4.  Gene #19: '20q gain' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
20Q GAIN CNV 15 6 0.5 - 41.1 (12.4)
20Q GAIN WILD-TYPE 191 45 0.0 - 211.2 (13.4)

Figure S4.  Get High-res Image Gene #19: '20q gain' versus Clinical Feature #1: 'Time to Death'

'1p loss' versus 'HISTOLOGICAL.TYPE'

P value = 4.61e-19 (Fisher's exact test), Q value = 1.3e-16

Table S5.  Gene #21: '1p loss' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 63 54 89
1P LOSS CNV 2 6 57
1P LOSS WILD-TYPE 61 48 32

Figure S5.  Get High-res Image Gene #21: '1p loss' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'3p loss' versus 'AGE'

P value = 1.04e-05 (t-test), Q value = 0.0029

Table S6.  Gene #25: '3p loss' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 207 43.1 (13.4)
3P LOSS CNV 4 31.0 (2.2)
3P LOSS WILD-TYPE 203 43.3 (13.4)

Figure S6.  Get High-res Image Gene #25: '3p loss' versus Clinical Feature #2: 'AGE'

'6p loss' versus 'Time to Death'

P value = 5.29e-05 (logrank test), Q value = 0.015

Table S7.  Gene #31: '6p loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
6P LOSS CNV 5 2 3.0 - 13.4 (6.4)
6P LOSS WILD-TYPE 201 49 0.0 - 211.2 (14.4)

Figure S7.  Get High-res Image Gene #31: '6p loss' versus Clinical Feature #1: 'Time to Death'

'10p loss' versus 'Time to Death'

P value = 8.93e-11 (logrank test), Q value = 2.6e-08

Table S8.  Gene #35: '10p loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
10P LOSS CNV 30 17 0.1 - 134.3 (8.6)
10P LOSS WILD-TYPE 176 34 0.0 - 211.2 (14.6)

Figure S8.  Get High-res Image Gene #35: '10p loss' versus Clinical Feature #1: 'Time to Death'

'10p loss' versus 'AGE'

P value = 6.05e-08 (t-test), Q value = 1.7e-05

Table S9.  Gene #35: '10p loss' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 207 43.1 (13.4)
10P LOSS CNV 30 54.9 (10.4)
10P LOSS WILD-TYPE 177 41.1 (12.9)

Figure S9.  Get High-res Image Gene #35: '10p loss' versus Clinical Feature #2: 'AGE'

'10p loss' versus 'HISTOLOGICAL.TYPE'

P value = 0.00083 (Fisher's exact test), Q value = 0.23

Table S10.  Gene #35: '10p loss' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 63 54 89
10P LOSS CNV 18 6 6
10P LOSS WILD-TYPE 45 48 83

Figure S10.  Get High-res Image Gene #35: '10p loss' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'10q loss' versus 'Time to Death'

P value = 1.88e-10 (logrank test), Q value = 5.3e-08

Table S11.  Gene #36: '10q loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
10Q LOSS CNV 31 17 0.1 - 134.3 (8.8)
10Q LOSS WILD-TYPE 175 34 0.0 - 211.2 (14.7)

Figure S11.  Get High-res Image Gene #36: '10q loss' versus Clinical Feature #1: 'Time to Death'

'10q loss' versus 'AGE'

P value = 3.06e-08 (t-test), Q value = 8.7e-06

Table S12.  Gene #36: '10q loss' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 207 43.1 (13.4)
10Q LOSS CNV 31 54.8 (10.3)
10Q LOSS WILD-TYPE 176 41.0 (12.9)

Figure S12.  Get High-res Image Gene #36: '10q loss' versus Clinical Feature #2: 'AGE'

'10q loss' versus 'HISTOLOGICAL.TYPE'

P value = 0.000389 (Fisher's exact test), Q value = 0.11

Table S13.  Gene #36: '10q loss' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 63 54 89
10Q LOSS CNV 19 6 6
10Q LOSS WILD-TYPE 44 48 83

Figure S13.  Get High-res Image Gene #36: '10q loss' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'11q loss' versus 'Time to Death'

P value = 0.000569 (logrank test), Q value = 0.16

Table S14.  Gene #38: '11q loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
11Q LOSS CNV 4 3 6.0 - 41.1 (13.2)
11Q LOSS WILD-TYPE 202 48 0.0 - 211.2 (13.4)

Figure S14.  Get High-res Image Gene #38: '11q loss' versus Clinical Feature #1: 'Time to Death'

'14q loss' versus 'Time to Death'

P value = 0.000835 (logrank test), Q value = 0.23

Table S15.  Gene #41: '14q loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
14Q LOSS CNV 22 10 4.1 - 80.0 (9.2)
14Q LOSS WILD-TYPE 184 41 0.0 - 211.2 (13.9)

Figure S15.  Get High-res Image Gene #41: '14q loss' versus Clinical Feature #1: 'Time to Death'

'19q loss' versus 'HISTOLOGICAL.TYPE'

P value = 2.67e-14 (Fisher's exact test), Q value = 7.7e-12

Table S16.  Gene #47: '19q loss' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 63 54 89
19Q LOSS CNV 8 7 58
19Q LOSS WILD-TYPE 55 47 31

Figure S16.  Get High-res Image Gene #47: '19q loss' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'22q loss' versus 'Time to Death'

P value = 3.89e-06 (logrank test), Q value = 0.0011

Table S17.  Gene #49: '22q loss' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 206 51 0.0 - 211.2 (13.4)
22Q LOSS CNV 14 7 0.1 - 46.6 (11.9)
22Q LOSS WILD-TYPE 192 44 0.0 - 211.2 (13.9)

Figure S17.  Get High-res Image Gene #49: '22q loss' versus Clinical Feature #1: 'Time to Death'

Methods & Data
Input

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

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

  • Number of patients = 207

  • Number of significantly arm-level cnvs = 50

  • Number of selected clinical features = 6

  • 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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