Correlation between copy number variation genes (focal events) and molecular subtypes
Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (Primary solid tumor)
28 January 2016  |  analyses__2016_01_28
Maintainer Information
Citation Information
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2016): Correlation between copy number variation genes (focal events) and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1DZ07P9
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 39 focal events and 10 molecular subtypes across 48 patients, 12 significant findings detected with P value < 0.05 and Q value < 0.25.

  • amp_2p16.1 cnv correlated to 'MRNASEQ_CNMF'.

  • amp_3q27.3 cnv correlated to 'CN_CNMF'.

  • amp_3q29 cnv correlated to 'CN_CNMF'.

  • amp_7p22.3 cnv correlated to 'CN_CNMF'.

  • amp_7q21.3 cnv correlated to 'CN_CNMF'.

  • amp_18q21.2 cnv correlated to 'CN_CNMF'.

  • del_5q33.3 cnv correlated to 'MIRSEQ_CHIERARCHICAL'.

  • del_8q12.1 cnv correlated to 'CN_CNMF'.

  • del_9p21.3 cnv correlated to 'METHLYATION_CNMF' and 'MIRSEQ_MATURE_CHIERARCHICAL'.

  • del_10q23.31 cnv correlated to 'MIRSEQ_MATURE_CHIERARCHICAL'.

  • del_12p13.2 cnv correlated to 'CN_CNMF'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between significant copy number variation of 39 focal events and 10 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 12 significant findings detected.

Clinical
Features
CN
CNMF
METHLYATION
CNMF
RPPA
CNMF
RPPA
CHIERARCHICAL
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 Fisher's exact test Fisher's exact test
del 9p21 3 17 (35%) 31 0.00855
(0.252)
0.00074
(0.0913)
0.739
(0.961)
0.711
(0.952)
0.00906
(0.252)
0.0911
(0.515)
0.18
(0.617)
0.0293
(0.382)
0.0206
(0.362)
0.00382
(0.166)
amp 2p16 1 16 (33%) 32 0.546
(0.839)
0.0992
(0.517)
0.0664
(0.504)
0.271
(0.723)
0.00117
(0.0913)
0.0505
(0.504)
0.398
(0.779)
0.0123
(0.286)
0.0383
(0.465)
0.382
(0.779)
amp 3q27 3 14 (29%) 34 0.00039
(0.076)
0.465
(0.806)
0.512
(0.823)
0.252
(0.691)
0.117
(0.537)
0.0971
(0.517)
0.181
(0.617)
0.292
(0.735)
0.696
(0.952)
0.531
(0.825)
amp 3q29 15 (31%) 33 0.00019
(0.0741)
0.332
(0.761)
0.418
(0.78)
0.109
(0.537)
0.147
(0.606)
0.0739
(0.504)
0.261
(0.712)
0.296
(0.737)
0.693
(0.952)
0.782
(0.989)
amp 7p22 3 16 (33%) 32 0.00448
(0.167)
0.854
(1.00)
0.815
(1.00)
0.761
(0.981)
0.129
(0.57)
0.0702
(0.504)
0.68
(0.952)
0.886
(1.00)
0.438
(0.794)
0.737
(0.961)
amp 7q21 3 15 (31%) 33 0.0026
(0.127)
0.436
(0.794)
0.824
(1.00)
1
(1.00)
0.196
(0.617)
0.422
(0.783)
0.679
(0.952)
0.887
(1.00)
0.0995
(0.517)
0.41
(0.78)
amp 18q21 2 16 (33%) 32 0.00109
(0.0913)
0.392
(0.779)
0.015
(0.307)
0.715
(0.952)
0.526
(0.823)
0.384
(0.779)
0.0859
(0.507)
0.0289
(0.382)
0.266
(0.721)
0.0488
(0.503)
del 5q33 3 4 (8%) 44 0.645
(0.942)
0.38
(0.779)
0.17
(0.617)
0.173
(0.617)
0.307
(0.737)
0.0075
(0.244)
0.0803
(0.504)
0.196
(0.617)
del 8q12 1 9 (19%) 39 0.00472
(0.167)
0.32
(0.747)
0.291
(0.735)
0.0441
(0.503)
0.107
(0.537)
0.952
(1.00)
0.15
(0.606)
0.407
(0.78)
0.629
(0.929)
0.0812
(0.504)
del 10q23 31 7 (15%) 41 0.469
(0.806)
0.0792
(0.504)
0.0262
(0.382)
0.127
(0.57)
0.0548
(0.504)
0.246
(0.691)
0.289
(0.735)
0.00185
(0.109)
del 12p13 2 8 (17%) 40 0.00195
(0.109)
0.11
(0.537)
0.922
(1.00)
0.815
(1.00)
0.236
(0.675)
0.941
(1.00)
0.395
(0.779)
0.955
(1.00)
0.506
(0.823)
0.202
(0.624)
amp 1q24 2 16 (33%) 32 0.843
(1.00)
0.445
(0.797)
0.456
(0.806)
0.512
(0.823)
0.454
(0.805)
0.509
(0.823)
0.641
(0.939)
0.459
(0.806)
0.968
(1.00)
0.904
(1.00)
amp 5p13 1 8 (17%) 40 0.279
(0.727)
0.0829
(0.504)
0.976
(1.00)
1
(1.00)
0.137
(0.588)
0.852
(1.00)
1
(1.00)
0.591
(0.894)
0.938
(1.00)
0.448
(0.797)
amp 8q24 23 14 (29%) 34 0.518
(0.823)
0.435
(0.794)
0.973
(1.00)
0.783
(0.989)
0.211
(0.629)
0.354
(0.765)
0.0614
(0.504)
0.196
(0.617)
0.196
(0.617)
0.203
(0.624)
amp 12q21 1 14 (29%) 34 0.077
(0.504)
0.207
(0.624)
0.953
(1.00)
0.714
(0.952)
0.164
(0.617)
0.636
(0.935)
0.525
(0.823)
0.0728
(0.504)
0.0686
(0.504)
0.114
(0.537)
amp 16p12 2 10 (21%) 38 0.393
(0.779)
0.118
(0.537)
0.306
(0.737)
0.859
(1.00)
0.0225
(0.362)
0.0876
(0.507)
0.287
(0.735)
0.0488
(0.503)
0.195
(0.617)
0.158
(0.609)
amp 19q13 43 10 (21%) 38 0.049
(0.503)
0.596
(0.895)
0.823
(1.00)
1
(1.00)
0.0836
(0.504)
0.882
(1.00)
0.366
(0.771)
0.279
(0.727)
0.279
(0.727)
0.0158
(0.307)
amp xq28 8 (17%) 40 0.523
(0.823)
0.208
(0.624)
0.975
(1.00)
0.443
(0.795)
0.172
(0.617)
0.368
(0.771)
0.0983
(0.517)
0.0232
(0.362)
0.223
(0.651)
0.413
(0.78)
del 1p36 32 11 (23%) 37 0.722
(0.957)
0.515
(0.823)
0.71
(0.952)
0.546
(0.839)
0.154
(0.606)
0.416
(0.78)
0.916
(1.00)
0.702
(0.952)
0.404
(0.779)
1
(1.00)
del 1p13 1 12 (25%) 36 0.392
(0.779)
0.667
(0.95)
0.953
(1.00)
0.346
(0.765)
0.657
(0.95)
0.838
(1.00)
0.414
(0.78)
0.765
(0.981)
0.922
(1.00)
0.251
(0.691)
del 1q43 10 (21%) 38 0.188
(0.617)
0.887
(1.00)
0.308
(0.737)
0.0475
(0.503)
0.497
(0.823)
0.319
(0.747)
1
(1.00)
0.842
(1.00)
1
(1.00)
0.896
(1.00)
del 2q23 1 8 (17%) 40 0.224
(0.651)
0.899
(1.00)
0.412
(0.78)
0.132
(0.574)
0.701
(0.952)
0.562
(0.856)
0.595
(0.895)
0.523
(0.823)
0.469
(0.806)
1
(1.00)
del 3p21 31 8 (17%) 40 0.669
(0.95)
0.353
(0.765)
0.806
(1.00)
0.71
(0.952)
0.848
(1.00)
0.146
(0.606)
0.0885
(0.507)
0.776
(0.987)
0.0393
(0.465)
0.0347
(0.436)
del 4q35 1 10 (21%) 38 0.0627
(0.504)
0.491
(0.823)
0.167
(0.617)
0.346
(0.765)
0.794
(1)
0.692
(0.952)
0.67
(0.95)
0.152
(0.606)
0.355
(0.765)
0.287
(0.735)
del 6p21 32 6 (12%) 42 1
(1.00)
0.353
(0.765)
0.347
(0.765)
0.219
(0.646)
0.734
(0.961)
0.485
(0.823)
0.497
(0.823)
0.522
(0.823)
0.114
(0.537)
0.298
(0.737)
del 6q14 1 17 (35%) 31 0.0817
(0.504)
0.118
(0.537)
0.5
(0.823)
0.521
(0.823)
0.94
(1.00)
0.945
(1.00)
0.179
(0.617)
0.178
(0.617)
0.196
(0.617)
0.69
(0.952)
del 6q22 32 16 (33%) 32 0.0978
(0.517)
0.0123
(0.286)
0.749
(0.971)
0.891
(1.00)
0.239
(0.675)
0.707
(0.952)
0.342
(0.765)
0.367
(0.771)
0.327
(0.76)
0.143
(0.606)
del 6q23 3 16 (33%) 32 0.0132
(0.286)
0.0214
(0.362)
0.0681
(0.504)
0.0751
(0.504)
0.227
(0.656)
0.184
(0.617)
0.075
(0.504)
0.165
(0.617)
0.195
(0.617)
0.605
(0.9)
del 7q33 5 (10%) 43 0.441
(0.795)
0.619
(0.919)
0.0197
(0.362)
0.307
(0.737)
0.858
(1.00)
0.178
(0.617)
0.912
(1.00)
0.911
(1.00)
del 8p23 2 12 (25%) 36 0.132
(0.574)
0.584
(0.886)
0.738
(0.961)
0.512
(0.823)
0.401
(0.779)
1
(1.00)
0.777
(0.987)
0.0797
(0.504)
0.763
(0.981)
0.6
(0.897)
del 13q14 2 7 (15%) 41 1
(1.00)
0.0788
(0.504)
0.394
(0.779)
0.274
(0.727)
0.0129
(0.286)
0.377
(0.779)
0.467
(0.806)
0.249
(0.691)
0.238
(0.675)
0.114
(0.537)
del 15q21 1 13 (27%) 35 0.682
(0.952)
0.084
(0.504)
0.843
(1.00)
0.731
(0.961)
0.533
(0.825)
0.305
(0.737)
0.915
(1.00)
0.665
(0.95)
0.838
(1.00)
0.208
(0.624)
del 16p13 13 6 (12%) 42 0.503
(0.823)
0.812
(1.00)
0.148
(0.606)
0.155
(0.606)
0.299
(0.737)
0.81
(1.00)
0.67
(0.95)
0.029
(0.382)
0.315
(0.745)
0.895
(1.00)
del 16q23 1 5 (10%) 43 0.112
(0.537)
0.341
(0.765)
0.27
(0.723)
0.367
(0.771)
0.487
(0.823)
0.708
(0.952)
0.0714
(0.504)
0.166
(0.617)
0.342
(0.765)
0.402
(0.779)
del 17p13 1 13 (27%) 35 0.0644
(0.504)
0.654
(0.95)
0.806
(1.00)
0.883
(1.00)
0.367
(0.771)
0.962
(1.00)
1
(1.00)
0.508
(0.823)
0.404
(0.779)
0.311
(0.739)
del 17q24 1 8 (17%) 40 0.392
(0.779)
0.0964
(0.517)
0.342
(0.765)
0.169
(0.617)
0.0555
(0.504)
0.11
(0.537)
0.7
(0.952)
0.0288
(0.382)
0.08
(0.504)
0.0676
(0.504)
del 19p13 2 4 (8%) 44 0.503
(0.823)
0.897
(1.00)
0.183
(0.617)
0.199
(0.62)
0.678
(0.952)
0.425
(0.786)
1
(1.00)
0.897
(1.00)
del 19q13 2 5 (10%) 43 0.836
(1.00)
0.428
(0.787)
0.899
(1.00)
1
(1.00)
0.86
(1.00)
0.661
(0.95)
1
(1.00)
0.724
(0.957)
del 22q13 31 7 (15%) 41 0.331
(0.761)
0.558
(0.853)
0.528
(0.823)
0.836
(1.00)
0.153
(0.606)
0.467
(0.806)
0.776
(0.987)
0.908
(1.00)
0.4
(0.779)
1
(1.00)
'amp_2p16.1' versus 'MRNASEQ_CNMF'

P value = 0.00117 (Fisher's exact test), Q value = 0.091

Table S1.  Gene #2: 'amp_2p16.1' versus Molecular Subtype #5: 'MRNASEQ_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5 CLUS_6
ALL 10 12 9 3 8 6
AMP PEAK 2(2P16.1) MUTATED 4 1 1 2 7 1
AMP PEAK 2(2P16.1) WILD-TYPE 6 11 8 1 1 5

Figure S1.  Get High-res Image Gene #2: 'amp_2p16.1' versus Molecular Subtype #5: 'MRNASEQ_CNMF'

'amp_3q27.3' versus 'CN_CNMF'

P value = 0.00039 (Fisher's exact test), Q value = 0.076

Table S2.  Gene #3: 'amp_3q27.3' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 7 21
AMP PEAK 3(3Q27.3) MUTATED 1 1 12
AMP PEAK 3(3Q27.3) WILD-TYPE 19 6 9

Figure S2.  Get High-res Image Gene #3: 'amp_3q27.3' versus Molecular Subtype #1: 'CN_CNMF'

'amp_3q29' versus 'CN_CNMF'

P value = 0.00019 (Fisher's exact test), Q value = 0.074

Table S3.  Gene #4: 'amp_3q29' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 7 21
AMP PEAK 4(3Q29) MUTATED 1 1 13
AMP PEAK 4(3Q29) WILD-TYPE 19 6 8

Figure S3.  Get High-res Image Gene #4: 'amp_3q29' versus Molecular Subtype #1: 'CN_CNMF'

'amp_7p22.3' versus 'CN_CNMF'

P value = 0.00448 (Fisher's exact test), Q value = 0.17

Table S4.  Gene #6: 'amp_7p22.3' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 7 21
AMP PEAK 6(7P22.3) MUTATED 2 2 12
AMP PEAK 6(7P22.3) WILD-TYPE 18 5 9

Figure S4.  Get High-res Image Gene #6: 'amp_7p22.3' versus Molecular Subtype #1: 'CN_CNMF'

'amp_7q21.3' versus 'CN_CNMF'

P value = 0.0026 (Fisher's exact test), Q value = 0.13

Table S5.  Gene #7: 'amp_7q21.3' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 7 21
AMP PEAK 7(7Q21.3) MUTATED 2 1 12
AMP PEAK 7(7Q21.3) WILD-TYPE 18 6 9

Figure S5.  Get High-res Image Gene #7: 'amp_7q21.3' versus Molecular Subtype #1: 'CN_CNMF'

'amp_18q21.2' versus 'CN_CNMF'

P value = 0.00109 (Fisher's exact test), Q value = 0.091

Table S6.  Gene #11: 'amp_18q21.2' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 7 21
AMP PEAK 12(18Q21.2) MUTATED 2 1 13
AMP PEAK 12(18Q21.2) WILD-TYPE 18 6 8

Figure S6.  Get High-res Image Gene #11: 'amp_18q21.2' versus Molecular Subtype #1: 'CN_CNMF'

'del_5q33.3' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.0075 (Fisher's exact test), Q value = 0.24

Table S7.  Gene #20: 'del_5q33.3' versus Molecular Subtype #8: 'MIRSEQ_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4 CLUS_5
ALL 9 12 8 12 6
DEL PEAK 7(5Q33.3) MUTATED 0 0 3 0 1
DEL PEAK 7(5Q33.3) WILD-TYPE 9 12 5 12 5

Figure S7.  Get High-res Image Gene #20: 'del_5q33.3' versus Molecular Subtype #8: 'MIRSEQ_CHIERARCHICAL'

'del_8q12.1' versus 'CN_CNMF'

P value = 0.00472 (Fisher's exact test), Q value = 0.17

Table S8.  Gene #27: 'del_8q12.1' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 7 21
DEL PEAK 14(8Q12.1) MUTATED 0 1 8
DEL PEAK 14(8Q12.1) WILD-TYPE 20 6 13

Figure S8.  Get High-res Image Gene #27: 'del_8q12.1' versus Molecular Subtype #1: 'CN_CNMF'

'del_9p21.3' versus 'METHLYATION_CNMF'

P value = 0.00074 (Fisher's exact test), Q value = 0.091

Table S9.  Gene #28: 'del_9p21.3' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 9 13 19 7
DEL PEAK 15(9P21.3) MUTATED 0 3 13 1
DEL PEAK 15(9P21.3) WILD-TYPE 9 10 6 6

Figure S9.  Get High-res Image Gene #28: 'del_9p21.3' versus Molecular Subtype #2: 'METHLYATION_CNMF'

'del_9p21.3' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.00382 (Fisher's exact test), Q value = 0.17

Table S10.  Gene #28: 'del_9p21.3' versus Molecular Subtype #10: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 8 15 5 14
DEL PEAK 15(9P21.3) MUTATED 2 2 5 6
DEL PEAK 15(9P21.3) WILD-TYPE 6 13 0 8

Figure S10.  Get High-res Image Gene #28: 'del_9p21.3' versus Molecular Subtype #10: 'MIRSEQ_MATURE_CHIERARCHICAL'

'del_10q23.31' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.00185 (Fisher's exact test), Q value = 0.11

Table S11.  Gene #29: 'del_10q23.31' versus Molecular Subtype #10: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 8 15 5 14
DEL PEAK 16(10Q23.31) MUTATED 0 0 0 6
DEL PEAK 16(10Q23.31) WILD-TYPE 8 15 5 8

Figure S11.  Get High-res Image Gene #29: 'del_10q23.31' versus Molecular Subtype #10: 'MIRSEQ_MATURE_CHIERARCHICAL'

'del_12p13.2' versus 'CN_CNMF'

P value = 0.00195 (Fisher's exact test), Q value = 0.11

Table S12.  Gene #30: 'del_12p13.2' versus Molecular Subtype #1: 'CN_CNMF'

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 20 7 21
DEL PEAK 17(12P13.2) MUTATED 0 0 8
DEL PEAK 17(12P13.2) WILD-TYPE 20 7 13

Figure S12.  Get High-res Image Gene #30: 'del_12p13.2' versus Molecular Subtype #1: 'CN_CNMF'

Methods & Data
Input
  • Copy number data file = all_lesions.txt from GISTIC pipeline

  • Processed Copy number data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/DLBC-TP/22516373/transformed.cor.cli.txt

  • Molecular subtype file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_mergedClustering/DLBC-TP/22541055/DLBC-TP.transferedmergedcluster.txt

  • Number of patients = 48

  • Number of significantly focal cnvs = 39

  • Number of molecular subtypes = 10

  • 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)