Correlation between copy number variation genes (focal events) and molecular subtypes
Mesothelioma (Primary solid tumor)
17 October 2014  |  analyses__2014_10_17
Maintainer Information
Citation Information
doi:10.7908/C11R6PFB
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Correlation between copy number variation genes (focal events) and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C11R6PFB
Overview
Introduction

This pipeline computes the correlation between significant copy number variation (cnv focal) genes and molecular subtypes.

Summary

Testing the association between copy number variation 21 focal events and 8 molecular subtypes across 87 patients, 22 significant findings detected with P value < 0.05 and Q value < 0.25.

  • del_1p36.31 cnv correlated to 'CN_CNMF'.

  • del_1p21.3 cnv correlated to 'MRNASEQ_CNMF'.

  • del_3p21.1 cnv correlated to 'CN_CNMF',  'MRNASEQ_CNMF', and 'MIRSEQ_CHIERARCHICAL'.

  • del_4q26 cnv correlated to 'CN_CNMF' and 'MRNASEQ_CHIERARCHICAL'.

  • del_4q34.3 cnv correlated to 'CN_CNMF' and 'MRNASEQ_CHIERARCHICAL'.

  • del_5q23.2 cnv correlated to 'CN_CNMF'.

  • del_6q22.1 cnv correlated to 'CN_CNMF'.

  • del_6q26 cnv correlated to 'CN_CNMF'.

  • del_9p21.3 cnv correlated to 'CN_CNMF' and 'MRNASEQ_CHIERARCHICAL'.

  • del_11q23.2 cnv correlated to 'CN_CNMF'.

  • del_14q32.31 cnv correlated to 'CN_CNMF',  'MRNASEQ_CNMF', and 'MRNASEQ_CHIERARCHICAL'.

  • del_15q15.1 cnv correlated to 'CN_CNMF' and 'METHLYATION_CNMF'.

  • del_22q12.2 cnv correlated to 'CN_CNMF' and 'METHLYATION_CNMF'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 21 focal events and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 22 significant findings detected.

Clinical
Features 		CN
CNMF 		METHLYATION
CNMF 		MRNASEQ
CNMF 		MRNASEQ
CHIERARCHICAL 		MIRSEQ
CNMF 		MIRSEQ
CHIERARCHICAL 		MIRSEQ
MATURE
CNMF 		MIRSEQ
MATURE
CHIERARCHICAL
nCNV (%) nWild-Type Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
del 3p21 1 48 (55%) 39 0.00044
(0.0682) 		0.124
(1.00) 		0.00054
(0.0826) 		0.399
(1.00) 		0.258
(1.00) 		0.00058
(0.0876) 		0.5
(1.00) 		0.00402
(0.571)
del 14q32 31 39 (45%) 48 0.00016
(0.0256) 		0.314
(1.00) 		0.00055
(0.0836) 		1e-05
(0.00168) 		0.011
(1.00) 		0.0169
(1.00) 		0.0213
(1.00) 		0.027
(1.00)
del 4q26 38 (44%) 49 1e-05
(0.00168) 		0.0572
(1.00) 		0.00305
(0.436) 		0.00097
(0.145) 		0.37
(1.00) 		0.41
(1.00) 		0.872
(1.00) 		0.325
(1.00)
del 4q34 3 41 (47%) 46 1e-05
(0.00168) 		0.0168
(1.00) 		0.0507
(1.00) 		0.00024
(0.0377) 		0.237
(1.00) 		0.516
(1.00) 		0.582
(1.00) 		0.273
(1.00)
del 9p21 3 51 (59%) 36 1e-05
(0.00168) 		0.00893
(1.00) 		0.00851
(1.00) 		1e-05
(0.00168) 		1
(1.00) 		0.791
(1.00) 		0.215
(1.00) 		0.0208
(1.00)
del 15q15 1 28 (32%) 59 3e-05
(0.00486) 		0.00113
(0.167) 		0.0257
(1.00) 		0.146
(1.00) 		0.282
(1.00) 		0.509
(1.00) 		0.323
(1.00) 		0.32
(1.00)
del 22q12 2 68 (78%) 19 0.00099
(0.148) 		0.00016
(0.0256) 		0.0667
(1.00) 		0.0134
(1.00) 		0.941
(1.00) 		0.801
(1.00) 		0.0348
(1.00) 		0.166
(1.00)
del 1p36 31 33 (38%) 54 1e-05
(0.00168) 		0.185
(1.00) 		0.336
(1.00) 		0.0118
(1.00) 		0.0946
(1.00) 		0.128
(1.00) 		0.596
(1.00) 		0.223
(1.00)
del 1p21 3 37 (43%) 50 0.108
(1.00) 		0.0264
(1.00) 		0.00053
(0.0816) 		0.0145
(1.00) 		0.956
(1.00) 		0.226
(1.00) 		0.431
(1.00) 		0.216
(1.00)
del 5q23 2 17 (20%) 70 0.00021
(0.0332) 		0.379
(1.00) 		0.568
(1.00) 		0.212
(1.00) 		0.639
(1.00) 		0.862
(1.00) 		0.498
(1.00) 		0.567
(1.00)
del 6q22 1 41 (47%) 46 0.0014
(0.206) 		0.243
(1.00) 		0.132
(1.00) 		0.165
(1.00) 		0.914
(1.00) 		0.688
(1.00) 		0.208
(1.00) 		0.288
(1.00)
del 6q26 36 (41%) 51 7e-05
(0.0113) 		0.251
(1.00) 		0.649
(1.00) 		0.82
(1.00) 		0.639
(1.00) 		0.898
(1.00) 		0.376
(1.00) 		0.206
(1.00)
del 11q23 2 18 (21%) 69 0.00041
(0.064) 		0.713
(1.00) 		0.0294
(1.00) 		0.0451
(1.00) 		0.725
(1.00) 		0.552
(1.00) 		0.33
(1.00) 		0.0649
(1.00)
del 2q35 17 (20%) 70 0.09
(1.00) 		0.0546
(1.00) 		0.321
(1.00) 		0.00201
(0.291) 		0.432
(1.00) 		0.157
(1.00) 		0.0418
(1.00) 		0.267
(1.00)
del 8p23 2 18 (21%) 69 0.867
(1.00) 		0.726
(1.00) 		0.967
(1.00) 		0.946
(1.00) 		0.703
(1.00) 		0.0831
(1.00) 		0.486
(1.00) 		0.786
(1.00)
del 10p15 3 28 (32%) 59 0.00177
(0.258) 		0.00679
(0.957) 		0.0519
(1.00) 		0.0111
(1.00) 		1
(1.00) 		0.708
(1.00) 		0.302
(1.00) 		0.878
(1.00)
del 10q25 2 31 (36%) 56 0.00298
(0.429) 		0.00757
(1.00) 		0.43
(1.00) 		0.583
(1.00) 		0.691
(1.00) 		0.717
(1.00) 		0.117
(1.00) 		0.475
(1.00)
del 12p13 31 11 (13%) 76 0.118
(1.00) 		0.0126
(1.00) 		0.0275
(1.00) 		0.119
(1.00) 		0.273
(1.00) 		0.0869
(1.00) 		0.426
(1.00) 		0.295
(1.00)
del 13q14 11 43 (49%) 44 0.0295
(1.00) 		0.177
(1.00) 		0.56
(1.00) 		0.364
(1.00) 		0.957
(1.00) 		0.947
(1.00) 		0.123
(1.00) 		0.677
(1.00)
del 16p13 3 6 (7%) 81 0.0687
(1.00) 		0.238
(1.00) 		0.165
(1.00) 		0.0422
(1.00) 		1
(1.00) 		0.387
(1.00) 		1
(1.00) 		0.51
(1.00)
del 16q24 1 22 (25%) 65 0.0265
(1.00) 		0.674
(1.00) 		0.101
(1.00) 		0.218
(1.00) 		0.503
(1.00) 		0.837
(1.00) 		0.549
(1.00) 		0.364
(1.00)
'del_1p36.31' versus 'CN_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.0017

Table S1.  Gene #1: 'del_1p36.31' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 1(1P36.31) MUTATED 2 19 5 7
DEL PEAK 1(1P36.31) WILD-TYPE 21 7 19 7

Figure S1.  Get High-res Image Gene #1: 'del_1p36.31' versus Molecular Subtype #1: 'CN_CNMF'

'del_1p21.3' versus 'MRNASEQ_CNMF'

P value = 0.00053 (Fisher's exact test), Q value = 0.082

Table S2.  Gene #2: 'del_1p21.3' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 25 21 18 21
DEL PEAK 2(1P21.3) MUTATED 5 11 5 16
DEL PEAK 2(1P21.3) WILD-TYPE 20 10 13 5

Figure S2.  Get High-res Image Gene #2: 'del_1p21.3' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'del_3p21.1' versus 'CN_CNMF'

P value = 0.00044 (Fisher's exact test), Q value = 0.068

Table S3.  Gene #4: 'del_3p21.1' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 4(3P21.1) MUTATED 13 16 18 1
DEL PEAK 4(3P21.1) WILD-TYPE 10 10 6 13

Figure S3.  Get High-res Image Gene #4: 'del_3p21.1' versus Molecular Subtype #1: 'CN_CNMF'

'del_3p21.1' versus 'MRNASEQ_CNMF'

P value = 0.00054 (Fisher's exact test), Q value = 0.083

Table S4.  Gene #4: 'del_3p21.1' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 25 21 18 21
DEL PEAK 4(3P21.1) MUTATED 20 4 10 13
DEL PEAK 4(3P21.1) WILD-TYPE 5 17 8 8

Figure S4.  Get High-res Image Gene #4: 'del_3p21.1' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'del_3p21.1' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.00058 (Fisher's exact test), Q value = 0.088

Table S5.  Gene #4: 'del_3p21.1' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 9 23 19 12 13
DEL PEAK 4(3P21.1) MUTATED 8 7 8 7 12
DEL PEAK 4(3P21.1) WILD-TYPE 1 16 11 5 1

Figure S5.  Get High-res Image Gene #4: 'del_3p21.1' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

'del_4q26' versus 'CN_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.0017

Table S6.  Gene #5: 'del_4q26' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 5(4Q26) MUTATED 3 21 6 8
DEL PEAK 5(4Q26) WILD-TYPE 20 5 18 6

Figure S6.  Get High-res Image Gene #5: 'del_4q26' versus Molecular Subtype #1: 'CN_CNMF'

'del_4q26' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.00097 (Fisher's exact test), Q value = 0.15

Table S7.  Gene #5: 'del_4q26' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 35 13 16
DEL PEAK 5(4Q26) MUTATED 2 20 5 10
DEL PEAK 5(4Q26) WILD-TYPE 19 15 8 6

Figure S7.  Get High-res Image Gene #5: 'del_4q26' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'del_4q34.3' versus 'CN_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.0017

Table S8.  Gene #6: 'del_4q34.3' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 6(4Q34.3) MUTATED 3 22 7 9
DEL PEAK 6(4Q34.3) WILD-TYPE 20 4 17 5

Figure S8.  Get High-res Image Gene #6: 'del_4q34.3' versus Molecular Subtype #1: 'CN_CNMF'

'del_4q34.3' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.00024 (Fisher's exact test), Q value = 0.038

Table S9.  Gene #6: 'del_4q34.3' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 35 13 16
DEL PEAK 6(4Q34.3) MUTATED 2 23 5 10
DEL PEAK 6(4Q34.3) WILD-TYPE 19 12 8 6

Figure S9.  Get High-res Image Gene #6: 'del_4q34.3' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'del_5q23.2' versus 'CN_CNMF'

P value = 0.00021 (Fisher's exact test), Q value = 0.033

Table S10.  Gene #7: 'del_5q23.2' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 7(5Q23.2) MUTATED 0 10 7 0
DEL PEAK 7(5Q23.2) WILD-TYPE 23 16 17 14

Figure S10.  Get High-res Image Gene #7: 'del_5q23.2' versus Molecular Subtype #1: 'CN_CNMF'

'del_6q22.1' versus 'CN_CNMF'

P value = 0.0014 (Fisher's exact test), Q value = 0.21

Table S11.  Gene #8: 'del_6q22.1' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 8(6Q22.1) MUTATED 12 19 8 2
DEL PEAK 8(6Q22.1) WILD-TYPE 11 7 16 12

Figure S11.  Get High-res Image Gene #8: 'del_6q22.1' versus Molecular Subtype #1: 'CN_CNMF'

'del_6q26' versus 'CN_CNMF'

P value = 7e-05 (Fisher's exact test), Q value = 0.011

Table S12.  Gene #9: 'del_6q26' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 9(6Q26) MUTATED 11 19 4 2
DEL PEAK 9(6Q26) WILD-TYPE 12 7 20 12

Figure S12.  Get High-res Image Gene #9: 'del_6q26' versus Molecular Subtype #1: 'CN_CNMF'

'del_9p21.3' versus 'CN_CNMF'

P value = 1e-05 (Fisher's exact test), Q value = 0.0017

Table S13.  Gene #11: 'del_9p21.3' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 11(9P21.3) MUTATED 2 24 20 5
DEL PEAK 11(9P21.3) WILD-TYPE 21 2 4 9

Figure S13.  Get High-res Image Gene #11: 'del_9p21.3' versus Molecular Subtype #1: 'CN_CNMF'

'del_9p21.3' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1e-05 (Fisher's exact test), Q value = 0.0017

Table S14.  Gene #11: 'del_9p21.3' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 35 13 16
DEL PEAK 11(9P21.3) MUTATED 3 28 9 11
DEL PEAK 11(9P21.3) WILD-TYPE 18 7 4 5

Figure S14.  Get High-res Image Gene #11: 'del_9p21.3' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'del_11q23.2' versus 'CN_CNMF'

P value = 0.00041 (Fisher's exact test), Q value = 0.064

Table S15.  Gene #14: 'del_11q23.2' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 14(11Q23.2) MUTATED 0 3 10 5
DEL PEAK 14(11Q23.2) WILD-TYPE 23 23 14 9

Figure S15.  Get High-res Image Gene #14: 'del_11q23.2' versus Molecular Subtype #1: 'CN_CNMF'

'del_14q32.31' versus 'CN_CNMF'

P value = 0.00016 (Fisher's exact test), Q value = 0.026

Table S16.  Gene #17: 'del_14q32.31' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 17(14Q32.31) MUTATED 4 18 7 10
DEL PEAK 17(14Q32.31) WILD-TYPE 19 8 17 4

Figure S16.  Get High-res Image Gene #17: 'del_14q32.31' versus Molecular Subtype #1: 'CN_CNMF'

'del_14q32.31' versus 'MRNASEQ_CNMF'

P value = 0.00055 (Fisher's exact test), Q value = 0.084

Table S17.  Gene #17: 'del_14q32.31' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 25 21 18 21
DEL PEAK 17(14Q32.31) MUTATED 6 17 5 10
DEL PEAK 17(14Q32.31) WILD-TYPE 19 4 13 11

Figure S17.  Get High-res Image Gene #17: 'del_14q32.31' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

'del_14q32.31' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1e-05 (Fisher's exact test), Q value = 0.0017

Table S18.  Gene #17: 'del_14q32.31' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 21 35 13 16
DEL PEAK 17(14Q32.31) MUTATED 3 27 1 7
DEL PEAK 17(14Q32.31) WILD-TYPE 18 8 12 9

Figure S18.  Get High-res Image Gene #17: 'del_14q32.31' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

'del_15q15.1' versus 'CN_CNMF'

P value = 3e-05 (Fisher's exact test), Q value = 0.0049

Table S19.  Gene #18: 'del_15q15.1' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 18(15Q15.1) MUTATED 0 9 15 4
DEL PEAK 18(15Q15.1) WILD-TYPE 23 17 9 10

Figure S19.  Get High-res Image Gene #18: 'del_15q15.1' versus Molecular Subtype #1: 'CN_CNMF'

'del_15q15.1' versus 'METHLYATION_CNMF'

P value = 0.00113 (Fisher's exact test), Q value = 0.17

Table S20.  Gene #18: 'del_15q15.1' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 14 20 26 27
DEL PEAK 18(15Q15.1) MUTATED 1 12 11 4
DEL PEAK 18(15Q15.1) WILD-TYPE 13 8 15 23

Figure S20.  Get High-res Image Gene #18: 'del_15q15.1' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_22q12.2' versus 'CN_CNMF'

P value = 0.00099 (Fisher's exact test), Q value = 0.15

Table S21.  Gene #21: 'del_22q12.2' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 23 26 24 14
DEL PEAK 21(22Q12.2) MUTATED 12 23 23 10
DEL PEAK 21(22Q12.2) WILD-TYPE 11 3 1 4

Figure S21.  Get High-res Image Gene #21: 'del_22q12.2' versus Molecular Subtype #1: 'CN_CNMF'

'del_22q12.2' versus 'METHLYATION_CNMF'

P value = 0.00016 (Fisher's exact test), Q value = 0.026

Table S22.  Gene #21: 'del_22q12.2' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 14 20 26 27
DEL PEAK 21(22Q12.2) MUTATED 10 19 25 14
DEL PEAK 21(22Q12.2) WILD-TYPE 4 1 1 13

Figure S22.  Get High-res Image Gene #21: 'del_22q12.2' versus Molecular Subtype #2: 'METHLYATION_CNMF'

Methods & Data
Input

  • Copy number data file = transformed.cor.cli.txt

  • Molecular subtype file = MESO-TP.transferedmergedcluster.txt

  • Number of patients = 87

  • Number of significantly focal cnvs = 21

  • Number of molecular subtypes = 8

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

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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

References
[1] 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)
[2] 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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