Correlation between gene mutation status and selected clinical features
Glioblastoma Multiforme (Primary solid tumor)
22 February 2013  |  analyses__2013_02_22
Maintainer Information
Citation Information
doi:10.7908/C1TQ5ZQN
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 gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1TQ5ZQN
Overview
Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and selected clinical features.

Summary

Testing the association between mutation status of 114 genes and 5 clinical features across 276 patients, 2 significant findings detected with Q value < 0.25.

  • IDH1 mutation correlated to 'AGE'.

  • ATRX mutation correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 114 genes and 5 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER KARNOFSKY
PERFORMANCE
SCORE 		RADIATIONS
RADIATION
REGIMENINDICATION
nMutated (%) nWild-Type logrank test t-test Fisher's exact test t-test Fisher's exact test
IDH1 14 (5%) 262 0.00261
(1.00) 		7.95e-05
(0.0441) 		0.269
(1.00) 		0.0319
(1.00) 		0.00287
(1.00)
ATRX 16 (6%) 260 0.0494
(1.00) 		0.000217
(0.12) 		0.597
(1.00) 		0.0201
(1.00) 		0.0609
(1.00)
PIK3R1 32 (12%) 244 0.868
(1.00) 		0.558
(1.00) 		0.334
(1.00) 		0.889
(1.00) 		0.699
(1.00)
BRAF 4 (1%) 272 0.253
(1.00) 		0.195
(1.00) 		1
(1.00) 		0.166
(1.00) 		0.123
(1.00)
EGFR 75 (27%) 201 0.952
(1.00) 		0.449
(1.00) 		0.4
(1.00) 		0.406
(1.00) 		0.67
(1.00)
TP53 81 (29%) 195 0.0583
(1.00) 		0.137
(1.00) 		0.583
(1.00) 		0.00907
(1.00) 		0.269
(1.00)
PTEN 88 (32%) 188 0.778
(1.00) 		0.162
(1.00) 		0.503
(1.00) 		0.676
(1.00) 		0.0574
(1.00)
PIK3CA 30 (11%) 246 0.435
(1.00) 		0.938
(1.00) 		0.692
(1.00) 		0.796
(1.00) 		0.418
(1.00)
RB1 22 (8%) 254 0.111
(1.00) 		0.853
(1.00) 		0.818
(1.00) 		0.0207
(1.00) 		0.494
(1.00)
NF1 31 (11%) 245 0.623
(1.00) 		0.208
(1.00) 		0.844
(1.00) 		0.136
(1.00) 		0.69
(1.00)
SPTA1 27 (10%) 249 0.407
(1.00) 		0.121
(1.00) 		0.21
(1.00) 		0.434
(1.00) 		0.291
(1.00)
KRTAP4-11 9 (3%) 267 0.629
(1.00) 		0.397
(1.00) 		0.728
(1.00) 		0.843
(1.00) 		0.724
(1.00)
GABRA6 11 (4%) 265 0.915
(1.00) 		0.208
(1.00) 		1
(1.00) 		0.58
(1.00) 		1
(1.00)
KEL 15 (5%) 261 0.503
(1.00) 		0.383
(1.00) 		0.419
(1.00) 		0.104
(1.00) 		0.404
(1.00)
RPL5 8 (3%) 268 0.897
(1.00) 		0.846
(1.00) 		0.47
(1.00) 		0.881
(1.00) 		0.718
(1.00)
CDH18 11 (4%) 265 0.395
(1.00) 		0.504
(1.00) 		1
(1.00) 		0.546
(1.00) 		0.522
(1.00)
PRB2 5 (2%) 271 0.928
(1.00) 		0.17
(1.00) 		1
(1.00) 		0.000758
(0.418) 		1
(1.00)
SEMA3C 11 (4%) 265 0.0506
(1.00) 		0.978
(1.00) 		0.751
(1.00) 		0.751
(1.00) 		0.199
(1.00)
TPTE2 8 (3%) 268 0.266
(1.00) 		0.601
(1.00) 		1
(1.00) 		0.026
(1.00) 		0.455
(1.00)
ZNF844 6 (2%) 270 0.56
(1.00) 		0.809
(1.00) 		0.196
(1.00) 		0.84
(1.00) 		1
(1.00)
OR8K3 6 (2%) 270 0.704
(1.00) 		0.882
(1.00) 		0.42
(1.00) 		0.566
(1.00) 		0.668
(1.00)
OR5AR1 6 (2%) 270 0.413
(1.00) 		0.00681
(1.00) 		0.672
(1.00) 		0.0583
(1.00) 		0.422
(1.00)
STAG2 12 (4%) 264 0.0133
(1.00) 		0.921
(1.00) 		0.763
(1.00) 		0.091
(1.00) 		0.352
(1.00)
SEMG1 8 (3%) 268 0.967
(1.00) 		0.136
(1.00) 		0.715
(1.00) 		0.342
(1.00) 		0.131
(1.00)
CDC27 5 (2%) 271 0.201
(1.00) 		0.701
(1.00) 		0.359
(1.00) 		1
(1.00)
PDGFRA 11 (4%) 265 0.586
(1.00) 		0.0263
(1.00) 		1
(1.00) 		0.688
(1.00) 		0.522
(1.00)
SULT1B1 6 (2%) 270 0.0691
(1.00) 		0.969
(1.00) 		1
(1.00) 		0.874
(1.00) 		1
(1.00)
ADAM29 9 (3%) 267 0.68
(1.00) 		0.0529
(1.00) 		0.162
(1.00) 		0.874
(1.00) 		0.503
(1.00)
HEATR7B2 12 (4%) 264 0.994
(1.00) 		0.163
(1.00) 		0.545
(1.00) 		0.669
(1.00) 		0.118
(1.00)
COL1A2 11 (4%) 265 0.657
(1.00) 		0.305
(1.00) 		1
(1.00) 		0.715
(1.00) 		0.199
(1.00)
ABCC9 11 (4%) 265 0.976
(1.00) 		0.253
(1.00) 		0.218
(1.00) 		0.542
(1.00) 		0.522
(1.00)
NLRP5 12 (4%) 264 0.349
(1.00) 		0.99
(1.00) 		0.545
(1.00) 		0.0724
(1.00) 		1
(1.00)
CALCR 7 (3%) 269 0.0293
(1.00) 		0.0155
(1.00) 		1
(1.00) 		0.702
(1.00) 		1
(1.00)
LZTR1 10 (4%) 266 0.72
(1.00) 		0.273
(1.00) 		0.0985
(1.00) 		0.751
(1.00) 		0.324
(1.00)
QKI 5 (2%) 271 0.926
(1.00) 		0.825
(1.00) 		1
(1.00) 		0.494
(1.00) 		0.0512
(1.00)
ZPBP 5 (2%) 271 0.342
(1.00) 		0.982
(1.00) 		0.359
(1.00) 		0.84
(1.00) 		0.346
(1.00)
PSPH 5 (2%) 271 0.219
(1.00) 		0.362
(1.00) 		0.655
(1.00) 		0.914
(1.00) 		0.661
(1.00)
UGT2A3 6 (2%) 270 0.977
(1.00) 		0.815
(1.00) 		1
(1.00) 		0.84
(1.00) 		0.0952
(1.00)
WNT2 5 (2%) 271 0.376
(1.00) 		0.237
(1.00) 		0.0617
(1.00) 		0.717
(1.00) 		1
(1.00)
OR5D18 6 (2%) 270 0.159
(1.00) 		0.695
(1.00) 		0.672
(1.00) 		0.173
(1.00) 		1
(1.00)
ABCB1 10 (4%) 266 0.502
(1.00) 		0.114
(1.00) 		0.178
(1.00) 		0.48
(1.00) 		0.324
(1.00)
CXORF22 9 (3%) 267 0.937
(1.00) 		0.364
(1.00) 		0.295
(1.00) 		0.234
(1.00) 		0.503
(1.00)
C1ORF150 3 (1%) 273 0.682
(1.00) 		0.0919
(1.00) 		1
(1.00) 		0.247
(1.00) 		1
(1.00)
GPX5 4 (1%) 272 0.373
(1.00) 		0.285
(1.00) 		1
(1.00) 		0.888
(1.00) 		0.302
(1.00)
LRRC55 6 (2%) 270 0.0155
(1.00) 		0.552
(1.00) 		0.672
(1.00) 		0.0486
(1.00) 		1
(1.00)
DCAF12L2 8 (3%) 268 0.531
(1.00) 		0.716
(1.00) 		0.265
(1.00) 		0.69
(1.00) 		1
(1.00)
LRFN5 7 (3%) 269 0.0281
(1.00) 		0.399
(1.00) 		0.264
(1.00) 		0.323
(1.00) 		0.00797
(1.00)
LUM 4 (1%) 272 0.0826
(1.00) 		0.853
(1.00) 		1
(1.00) 		0.765
(1.00) 		0.612
(1.00)
MMP13 6 (2%) 270 0.629
(1.00) 		0.152
(1.00) 		1
(1.00) 		0.0271
(1.00) 		0.0952
(1.00)
UGT2B28 6 (2%) 270 0.768
(1.00) 		0.817
(1.00) 		0.42
(1.00) 		0.793
(1.00) 		1
(1.00)
OR5D13 5 (2%) 271 0.461
(1.00) 		0.434
(1.00) 		0.655
(1.00) 		0.661
(1.00)
ZNF99 6 (2%) 270 0.752
(1.00) 		0.719
(1.00) 		0.42
(1.00) 		0.809
(1.00) 		1
(1.00)
SLC5A7 6 (2%) 270 0.116
(1.00) 		0.659
(1.00) 		0.42
(1.00) 		0.342
(1.00) 		1
(1.00)
TRPV6 8 (3%) 268 0.929
(1.00) 		0.104
(1.00) 		1
(1.00) 		0.401
(1.00) 		0.0538
(1.00)
SEMA3E 7 (3%) 269 0.403
(1.00) 		0.644
(1.00) 		1
(1.00) 		0.566
(1.00) 		0.1
(1.00)
SLC26A3 6 (2%) 270 0.484
(1.00) 		0.357
(1.00) 		0.42
(1.00) 		0.566
(1.00) 		0.668
(1.00)
OR4D5 5 (2%) 271 0.601
(1.00) 		0.143
(1.00) 		0.162
(1.00) 		0.378
(1.00) 		0.346
(1.00)
TCHH 16 (6%) 260 0.354
(1.00) 		0.355
(1.00) 		0.427
(1.00) 		0.511
(1.00) 		0.189
(1.00)
CFHR4 5 (2%) 271 0.377
(1.00) 		0.99
(1.00) 		0.359
(1.00) 		0.981
(1.00) 		1
(1.00)
GABRB2 6 (2%) 270 0.281
(1.00) 		0.0297
(1.00) 		0.196
(1.00) 		0.36
(1.00) 		0.187
(1.00)
IL18RAP 5 (2%) 271 0.789
(1.00) 		0.19
(1.00) 		0.359
(1.00) 		0.286
(1.00) 		0.661
(1.00)
OGDH 3 (1%) 273 0.229
(1.00) 		0.311
(1.00) 		1
(1.00) 		0.292
(1.00) 		1
(1.00)
PCDH11X 8 (3%) 268 0.0923
(1.00) 		0.157
(1.00) 		0.47
(1.00) 		0.0226
(1.00) 		0.131
(1.00)
SPRYD5 6 (2%) 270 0.813
(1.00) 		0.829
(1.00) 		0.672
(1.00) 		0.566
(1.00) 		1
(1.00)
TGFA 4 (1%) 272 0.917
(1.00) 		0.37
(1.00) 		0.141
(1.00) 		1
(1.00)
OR5P2 4 (1%) 272 0.268
(1.00) 		0.123
(1.00) 		0.3
(1.00) 		0.000758
(0.418) 		0.612
(1.00)
FOXR2 5 (2%) 271 0.208
(1.00) 		0.95
(1.00) 		1
(1.00) 		0.84
(1.00) 		1
(1.00)
PSG8 6 (2%) 270 0.278
(1.00) 		0.472
(1.00) 		0.196
(1.00) 		0.853
(1.00) 		0.422
(1.00)
CNTNAP2 12 (4%) 264 0.825
(1.00) 		0.134
(1.00) 		0.366
(1.00) 		0.165
(1.00) 		1
(1.00)
GABRA1 5 (2%) 271 0.772
(1.00) 		0.927
(1.00) 		0.655
(1.00) 		0.247
(1.00) 		1
(1.00)
DYNC1I1 7 (3%) 269 0.0966
(1.00) 		0.438
(1.00) 		1
(1.00) 		0.0886
(1.00) 		0.697
(1.00)
KDR 8 (3%) 268 0.16
(1.00) 		0.827
(1.00) 		0.715
(1.00) 		0.881
(1.00) 		0.269
(1.00)
PODXL 3 (1%) 273 0.339
(1.00) 		0.213
(1.00) 		0.556
(1.00) 		0.129
(1.00) 		0.554
(1.00)
SCN9A 11 (4%) 265 0.0287
(1.00) 		0.25
(1.00) 		0.751
(1.00) 		0.242
(1.00) 		0.199
(1.00)
PIK3C2G 9 (3%) 267 0.126
(1.00) 		0.393
(1.00) 		0.295
(1.00) 		0.566
(1.00) 		0.284
(1.00)
AFM 6 (2%) 270 0.271
(1.00) 		0.398
(1.00) 		0.672
(1.00) 		0.363
(1.00) 		1
(1.00)
CARD6 7 (3%) 269 0.00681
(1.00) 		0.0289
(1.00) 		0.429
(1.00) 		0.945
(1.00) 		0.242
(1.00)
OR5K4 4 (1%) 272 0.2
(1.00) 		0.193
(1.00) 		1
(1.00) 		0.716
(1.00) 		0.612
(1.00)
KRTAP20-2 3 (1%) 273 0.509
(1.00) 		0.334
(1.00) 		1
(1.00) 		0.554
(1.00)
PODNL1 4 (1%) 272 0.102
(1.00) 		0.174
(1.00) 		0.625
(1.00) 		0.506
(1.00) 		0.123
(1.00)
POTEF 5 (2%) 271 0.971
(1.00) 		0.718
(1.00) 		1
(1.00) 		1
(1.00)
OTC 3 (1%) 273 0.114
(1.00) 		0.774
(1.00) 		0.556
(1.00) 		0.278
(1.00)
TRAT1 4 (1%) 272 0.131
(1.00) 		0.465
(1.00) 		1
(1.00) 		0.612
(1.00)
RBM47 8 (3%) 268 0.893
(1.00) 		0.525
(1.00) 		1
(1.00) 		0.414
(1.00) 		1
(1.00)
KLK6 3 (1%) 273 0.248
(1.00) 		0.224
(1.00) 		0.556
(1.00) 		0.554
(1.00)
KRTAP4-7 3 (1%) 273 0.454
(1.00) 		0.314
(1.00) 		0.301
(1.00) 		0.278
(1.00)
CDH9 8 (3%) 268 0.558
(1.00) 		0.59
(1.00) 		0.47
(1.00) 		0.467
(1.00) 		1
(1.00)
OR4P4 4 (1%) 272 0.944
(1.00) 		0.357
(1.00) 		1
(1.00) 		1
(1.00)
OR52M1 4 (1%) 272 0.966
(1.00) 		0.473
(1.00) 		1
(1.00) 		0.743
(1.00) 		1
(1.00)
ADAMTS16 8 (3%) 268 0.859
(1.00) 		0.561
(1.00) 		0.715
(1.00) 		0.0904
(1.00) 		0.269
(1.00)
GLT8D2 3 (1%) 273 0.12
(1.00) 		0.405
(1.00) 		1
(1.00) 		0.0412
(1.00)
KLF17 5 (2%) 271 0.00218
(1.00) 		0.3
(1.00) 		0.162
(1.00) 		0.446
(1.00) 		1
(1.00)
CDHR3 3 (1%) 273 0.255
(1.00) 		0.544
(1.00) 		1
(1.00) 		0.286
(1.00) 		0.554
(1.00)
CD3EAP 3 (1%) 273 0.864
(1.00) 		0.663
(1.00) 		1
(1.00) 		0.716
(1.00) 		1
(1.00)
OR8J3 4 (1%) 272 0.377
(1.00) 		0.58
(1.00) 		0.625
(1.00) 		0.661
(1.00) 		0.302
(1.00)
AP3S1 3 (1%) 273 0.247
(1.00) 		0.351
(1.00) 		0.301
(1.00) 		0.247
(1.00) 		0.554
(1.00)
CKMT1A 3 (1%) 273 0.491
(1.00) 		0.0428
(1.00) 		0.301
(1.00) 		0.861
(1.00) 		1
(1.00)
ST6GAL2 5 (2%) 271 0.882
(1.00) 		0.347
(1.00) 		0.0617
(1.00) 		0.0899
(1.00) 		0.661
(1.00)
F9 4 (1%) 272 0.0203
(1.00) 		0.559
(1.00) 		0.625
(1.00) 		1
(1.00)
SHB 3 (1%) 273 0.988
(1.00) 		0.649
(1.00) 		0.556
(1.00) 		0.000758
(0.418) 		0.554
(1.00)
RSPO3 3 (1%) 273 0.397
(1.00) 		0.766
(1.00) 		0.556
(1.00) 		0.278
(1.00)
TCN1 4 (1%) 272 0.913
(1.00) 		0.315
(1.00) 		0.625
(1.00) 		0.123
(1.00)
CDKN2C 3 (1%) 273 0.731
(1.00) 		0.576
(1.00) 		0.301
(1.00) 		1
(1.00)
DRD5 7 (3%) 269 0.631
(1.00) 		0.229
(1.00) 		1
(1.00) 		0.286
(1.00) 		1
(1.00)
FGA 6 (2%) 270 0.911
(1.00) 		0.359
(1.00) 		0.089
(1.00) 		0.36
(1.00) 		0.668
(1.00)
FGG 5 (2%) 271 0.411
(1.00) 		0.0715
(1.00) 		0.359
(1.00) 		0.286
(1.00) 		0.661
(1.00)
HCN1 11 (4%) 265 0.234
(1.00) 		0.834
(1.00) 		0.538
(1.00) 		0.566
(1.00) 		0.199
(1.00)
PAN3 6 (2%) 270 0.284
(1.00) 		0.47
(1.00) 		1
(1.00) 		0.763
(1.00) 		0.668
(1.00)
OR10G8 4 (1%) 272 0.87
(1.00) 		0.256
(1.00) 		0.625
(1.00) 		0.84
(1.00) 		0.612
(1.00)
PROKR2 6 (2%) 270 0.474
(1.00) 		0.0196
(1.00) 		1
(1.00) 		0.993
(1.00) 		0.668
(1.00)
AZGP1 4 (1%) 272 0.644
(1.00) 		0.84
(1.00) 		1
(1.00) 		1
(1.00)
CYP3A5 5 (2%) 271 0.313
(1.00) 		0.699
(1.00) 		0.359
(1.00) 		0.363
(1.00) 		1
(1.00)
HIST1H2BE 3 (1%) 273 0.732
(1.00) 		0.192
(1.00) 		0.301
(1.00) 		0.5
(1.00) 		1
(1.00)
PCMTD1 4 (1%) 272 0.953
(1.00) 		0.288
(1.00) 		0.3
(1.00) 		0.935
(1.00) 		0.302
(1.00)
'IDH1 MUTATION STATUS' versus 'AGE'

P value = 7.95e-05 (t-test), Q value = 0.044

Table S1.  Gene #4: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 276 61.1 (12.6)
IDH1 MUTATED 14 40.7 (14.4)
IDH1 WILD-TYPE 262 62.2 (11.5)

Figure S1.  Get High-res Image Gene #4: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'ATRX MUTATION STATUS' versus 'AGE'

P value = 0.000217 (t-test), Q value = 0.12

Table S2.  Gene #36: 'ATRX MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 276 61.1 (12.6)
ATRX MUTATED 16 43.3 (15.7)
ATRX WILD-TYPE 260 62.2 (11.5)

Figure S2.  Get High-res Image Gene #36: 'ATRX MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

  • Mutation data file = GBM-TP.mutsig.cluster.txt

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

  • Number of patients = 276

  • Number of significantly mutated genes = 114

  • Number of selected clinical features = 5

  • 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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