Correlation between gene mutation status and selected clinical features
Glioblastoma Multiforme (Primary solid tumor)
21 April 2013  |  analyses__2013_04_21
Maintainer Information
Citation Information
doi:10.7908/C1N014G8
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Glioblastoma Multiforme (Primary solid tumor cohort) - 21 April 2013: Correlation between gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1N014G8
Overview
Introduction

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

Summary

Testing the association between mutation status of 110 genes and 5 clinical features across 269 patients, 5 significant findings detected with Q value < 0.25.

  • IDH1 mutation correlated to 'AGE'.

  • PRB2 mutation correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

  • OR5W2 mutation correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

  • OR5P2 mutation correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

  • SHB mutation correlated to 'KARNOFSKY.PERFORMANCE.SCORE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 110 genes and 5 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 5 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 13 (5%) 256 0.00204
(1.00) 		0.000245
(0.131) 		0.386
(1.00) 		0.0655
(1.00) 		0.00514
(1.00)
PRB2 5 (2%) 264 0.918
(1.00) 		0.167
(1.00) 		1
(1.00) 		0.000423
(0.226) 		1
(1.00)
OR5W2 5 (2%) 264 0.394
(1.00) 		0.0763
(1.00) 		1
(1.00) 		0.000424
(0.226) 		0.166
(1.00)
OR5P2 4 (1%) 265 0.265
(1.00) 		0.12
(1.00) 		0.3
(1.00) 		0.000423
(0.226) 		0.613
(1.00)
SHB 3 (1%) 266 0.978
(1.00) 		0.621
(1.00) 		0.301
(1.00) 		0.000424
(0.226) 		0.554
(1.00)
PIK3R1 31 (12%) 238 0.747
(1.00) 		0.596
(1.00) 		0.431
(1.00) 		0.872
(1.00) 		0.551
(1.00)
BRAF 4 (1%) 265 0.242
(1.00) 		0.198
(1.00) 		1
(1.00) 		0.158
(1.00) 		0.124
(1.00)
EGFR 72 (27%) 197 0.791
(1.00) 		0.485
(1.00) 		0.254
(1.00) 		0.512
(1.00) 		0.665
(1.00)
PTEN 85 (32%) 184 0.632
(1.00) 		0.195
(1.00) 		0.588
(1.00) 		0.98
(1.00) 		0.0542
(1.00)
TP53 77 (29%) 192 0.0321
(1.00) 		0.159
(1.00) 		0.674
(1.00) 		0.00657
(1.00) 		0.322
(1.00)
PIK3CA 28 (10%) 241 0.577
(1.00) 		0.854
(1.00) 		0.836
(1.00) 		0.98
(1.00) 		0.534
(1.00)
RB1 22 (8%) 247 0.104
(1.00) 		0.822
(1.00) 		0.818
(1.00) 		0.0179
(1.00) 		0.492
(1.00)
NF1 28 (10%) 241 0.845
(1.00) 		0.289
(1.00) 		1
(1.00) 		0.18
(1.00) 		0.677
(1.00)
SPTA1 26 (10%) 243 0.533
(1.00) 		0.176
(1.00) 		0.29
(1.00) 		0.469
(1.00) 		0.279
(1.00)
KRTAP4-11 9 (3%) 260 0.627
(1.00) 		0.406
(1.00) 		0.728
(1.00) 		0.818
(1.00) 		0.724
(1.00)
GABRA6 11 (4%) 258 0.912
(1.00) 		0.22
(1.00) 		1
(1.00) 		0.607
(1.00) 		1
(1.00)
KEL 15 (6%) 254 0.512
(1.00) 		0.404
(1.00) 		0.417
(1.00) 		0.0925
(1.00) 		0.404
(1.00)
CDH18 11 (4%) 258 0.379
(1.00) 		0.527
(1.00) 		1
(1.00) 		0.567
(1.00) 		0.523
(1.00)
RPL5 7 (3%) 262 0.994
(1.00) 		0.784
(1.00) 		0.261
(1.00) 		0.558
(1.00) 		0.427
(1.00)
SEMA3C 11 (4%) 258 0.0541
(1.00) 		0.959
(1.00) 		0.751
(1.00) 		0.77
(1.00) 		0.2
(1.00)
TPTE2 8 (3%) 261 0.256
(1.00) 		0.585
(1.00) 		1
(1.00) 		0.0232
(1.00) 		0.456
(1.00)
ZNF844 6 (2%) 263 0.579
(1.00) 		0.821
(1.00) 		0.195
(1.00) 		0.872
(1.00) 		1
(1.00)
OR8K3 6 (2%) 263 0.695
(1.00) 		0.904
(1.00) 		0.421
(1.00) 		0.544
(1.00) 		0.668
(1.00)
OR5AR1 6 (2%) 263 0.426
(1.00) 		0.0071
(1.00) 		0.671
(1.00) 		0.0605
(1.00) 		0.424
(1.00)
STAG2 12 (4%) 257 0.0148
(1.00) 		0.949
(1.00) 		0.763
(1.00) 		0.0956
(1.00) 		0.353
(1.00)
SEMG1 8 (3%) 261 0.941
(1.00) 		0.142
(1.00) 		0.715
(1.00) 		0.33
(1.00) 		0.132
(1.00)
CDC27 5 (2%) 264 0.209
(1.00) 		0.69
(1.00) 		0.358
(1.00) 		1
(1.00)
PDGFRA 11 (4%) 258 0.59
(1.00) 		0.0282
(1.00) 		1
(1.00) 		0.719
(1.00) 		0.523
(1.00)
ADAM29 9 (3%) 260 0.668
(1.00) 		0.0551
(1.00) 		0.162
(1.00) 		0.825
(1.00) 		0.502
(1.00)
SULT1B1 6 (2%) 263 0.0779
(1.00) 		0.984
(1.00) 		1
(1.00) 		0.825
(1.00) 		1
(1.00)
ABCC9 11 (4%) 258 0.968
(1.00) 		0.267
(1.00) 		0.216
(1.00) 		0.52
(1.00) 		0.523
(1.00)
NLRP5 12 (4%) 257 0.334
(1.00) 		0.964
(1.00) 		0.545
(1.00) 		0.0655
(1.00) 		1
(1.00)
LZTR1 10 (4%) 259 0.705
(1.00) 		0.285
(1.00) 		0.0989
(1.00) 		0.77
(1.00) 		0.326
(1.00)
CALCR 7 (3%) 262 0.0298
(1.00) 		0.0162
(1.00) 		1
(1.00) 		0.718
(1.00) 		1
(1.00)
QKI 5 (2%) 264 0.92
(1.00) 		0.813
(1.00) 		1
(1.00) 		0.527
(1.00) 		0.0521
(1.00)
ZPBP 5 (2%) 264 0.35
(1.00) 		0.994
(1.00) 		0.358
(1.00) 		0.872
(1.00) 		0.347
(1.00)
PSPH 5 (2%) 264 0.207
(1.00) 		0.374
(1.00) 		0.656
(1.00) 		0.932
(1.00) 		0.661
(1.00)
UGT2A3 6 (2%) 263 0.969
(1.00) 		0.841
(1.00) 		1
(1.00) 		0.872
(1.00) 		0.0945
(1.00)
WNT2 5 (2%) 264 0.36
(1.00) 		0.244
(1.00) 		0.0606
(1.00) 		0.685
(1.00) 		1
(1.00)
OR5D18 6 (2%) 263 0.174
(1.00) 		0.716
(1.00) 		0.671
(1.00) 		0.179
(1.00) 		1
(1.00)
ABCB1 10 (4%) 259 0.498
(1.00) 		0.11
(1.00) 		0.177
(1.00) 		0.455
(1.00) 		0.326
(1.00)
COL1A2 10 (4%) 259 0.751
(1.00) 		0.108
(1.00) 		1
(1.00) 		0.983
(1.00) 		0.326
(1.00)
ATRX 15 (6%) 254 0.045
(1.00) 		0.000576
(0.305) 		0.417
(1.00) 		0.0429
(1.00) 		0.0945
(1.00)
C1ORF150 3 (1%) 266 0.67
(1.00) 		0.0936
(1.00) 		1
(1.00) 		0.24
(1.00) 		1
(1.00)
LRRC55 6 (2%) 263 0.0165
(1.00) 		0.518
(1.00) 		0.671
(1.00) 		0.0451
(1.00) 		1
(1.00)
DCAF12L2 8 (3%) 261 0.536
(1.00) 		0.691
(1.00) 		0.265
(1.00) 		0.713
(1.00) 		1
(1.00)
LRFN5 7 (3%) 262 0.0282
(1.00) 		0.412
(1.00) 		0.261
(1.00) 		0.331
(1.00) 		0.00817
(1.00)
LUM 4 (1%) 265 0.0891
(1.00) 		0.845
(1.00) 		1
(1.00) 		0.752
(1.00) 		0.613
(1.00)
MMP13 6 (2%) 263 0.608
(1.00) 		0.157
(1.00) 		1
(1.00) 		0.0258
(1.00) 		0.0945
(1.00)
HEATR7B2 11 (4%) 258 0.885
(1.00) 		0.0614
(1.00) 		0.751
(1.00) 		0.979
(1.00) 		0.2
(1.00)
UGT2B28 6 (2%) 263 0.774
(1.00) 		0.828
(1.00) 		0.421
(1.00) 		0.804
(1.00) 		1
(1.00)
OR5D13 5 (2%) 264 0.461
(1.00) 		0.427
(1.00) 		0.656
(1.00) 		0.661
(1.00)
ZNF99 6 (2%) 263 0.752
(1.00) 		0.759
(1.00) 		0.421
(1.00) 		0.824
(1.00) 		1
(1.00)
SLC5A7 6 (2%) 263 0.128
(1.00) 		0.675
(1.00) 		0.421
(1.00) 		0.33
(1.00) 		1
(1.00)
SEMA3E 7 (3%) 262 0.396
(1.00) 		0.661
(1.00) 		1
(1.00) 		0.544
(1.00) 		0.1
(1.00)
TCHH 16 (6%) 253 0.351
(1.00) 		0.337
(1.00) 		0.427
(1.00) 		0.472
(1.00) 		0.188
(1.00)
SLC26A3 6 (2%) 263 0.497
(1.00) 		0.345
(1.00) 		0.421
(1.00) 		0.544
(1.00) 		0.668
(1.00)
GABRB2 6 (2%) 263 0.274
(1.00) 		0.0308
(1.00) 		0.195
(1.00) 		0.372
(1.00) 		0.188
(1.00)
CFHR4 5 (2%) 264 0.371
(1.00) 		0.996
(1.00) 		0.358
(1.00) 		0.977
(1.00) 		1
(1.00)
IL18RAP 5 (2%) 264 0.778
(1.00) 		0.195
(1.00) 		0.358
(1.00) 		0.294
(1.00) 		0.661
(1.00)
OGDH 3 (1%) 266 0.245
(1.00) 		0.317
(1.00) 		1
(1.00) 		0.297
(1.00) 		1
(1.00)
PCDH11X 8 (3%) 261 0.0982
(1.00) 		0.161
(1.00) 		0.468
(1.00) 		0.0237
(1.00) 		0.132
(1.00)
SPRYD5 6 (2%) 263 0.8
(1.00) 		0.821
(1.00) 		0.671
(1.00) 		0.544
(1.00) 		1
(1.00)
TGFA 4 (1%) 265 0.907
(1.00) 		0.378
(1.00) 		0.139
(1.00) 		1
(1.00)
UGT2B4 5 (2%) 264 0.348
(1.00) 		0.656
(1.00) 		0.656
(1.00) 		0.138
(1.00) 		0.347
(1.00)
FOXR2 5 (2%) 264 0.202
(1.00) 		0.957
(1.00) 		1
(1.00) 		0.872
(1.00) 		1
(1.00)
PSG8 6 (2%) 263 0.277
(1.00) 		0.479
(1.00) 		0.195
(1.00) 		0.865
(1.00) 		0.424
(1.00)
CNTNAP2 12 (4%) 257 0.818
(1.00) 		0.143
(1.00) 		0.364
(1.00) 		0.157
(1.00) 		1
(1.00)
PIK3C2G 9 (3%) 260 0.124
(1.00) 		0.411
(1.00) 		0.293
(1.00) 		0.544
(1.00) 		0.285
(1.00)
SCN9A 11 (4%) 258 0.0299
(1.00) 		0.26
(1.00) 		0.751
(1.00) 		0.255
(1.00) 		0.2
(1.00)
GABRA1 5 (2%) 264 0.788
(1.00) 		0.913
(1.00) 		0.656
(1.00) 		0.24
(1.00) 		1
(1.00)
DYNC1I1 7 (3%) 262 0.0997
(1.00) 		0.429
(1.00) 		1
(1.00) 		0.0853
(1.00) 		0.698
(1.00)
PODXL 3 (1%) 266 0.355
(1.00) 		0.224
(1.00) 		0.301
(1.00) 		0.126
(1.00) 		0.554
(1.00)
HCN1 10 (4%) 259 0.179
(1.00) 		0.837
(1.00) 		1
(1.00) 		0.158
(1.00) 		0.103
(1.00)
POTEF 5 (2%) 264 0.969
(1.00) 		0.702
(1.00) 		1
(1.00) 		1
(1.00)
CXORF22 8 (3%) 261 0.903
(1.00) 		0.548
(1.00) 		0.145
(1.00) 		0.455
(1.00) 		0.268
(1.00)
AFM 6 (2%) 263 0.277
(1.00) 		0.407
(1.00) 		0.671
(1.00) 		0.378
(1.00) 		1
(1.00)
KRTAP20-2 3 (1%) 266 0.519
(1.00) 		0.338
(1.00) 		1
(1.00) 		0.554
(1.00)
OTC 3 (1%) 266 0.123
(1.00) 		0.764
(1.00) 		0.301
(1.00) 		0.28
(1.00)
TRAT1 4 (1%) 265 0.141
(1.00) 		0.471
(1.00) 		1
(1.00) 		0.613
(1.00)
KLK6 3 (1%) 266 0.241
(1.00) 		0.221
(1.00) 		0.301
(1.00) 		0.554
(1.00)
OR4D5 4 (1%) 265 0.654
(1.00) 		0.0843
(1.00) 		0.3
(1.00) 		0.837
(1.00) 		0.124
(1.00)
GPX5 3 (1%) 266 0.356
(1.00) 		0.232
(1.00) 		1
(1.00) 		0.554
(1.00)
KRTAP4-7 3 (1%) 266 0.459
(1.00) 		0.317
(1.00) 		0.556
(1.00) 		0.28
(1.00)
CDH9 8 (3%) 261 0.534
(1.00) 		0.579
(1.00) 		0.468
(1.00) 		0.482
(1.00) 		1
(1.00)
CDHR3 3 (1%) 266 0.264
(1.00) 		0.553
(1.00) 		1
(1.00) 		0.294
(1.00) 		0.554
(1.00)
OR4P4 4 (1%) 265 0.952
(1.00) 		0.364
(1.00) 		1
(1.00) 		1
(1.00)
OR52M1 4 (1%) 265 0.969
(1.00) 		0.465
(1.00) 		1
(1.00) 		0.752
(1.00) 		1
(1.00)
KLF17 5 (2%) 264 0.00262
(1.00) 		0.306
(1.00) 		0.162
(1.00) 		0.469
(1.00) 		1
(1.00)
OR8J3 4 (1%) 265 0.384
(1.00) 		0.573
(1.00) 		0.624
(1.00) 		0.644
(1.00) 		0.301
(1.00)
AP3S1 3 (1%) 266 0.239
(1.00) 		0.348
(1.00) 		0.556
(1.00) 		0.24
(1.00) 		0.554
(1.00)
ST6GAL2 5 (2%) 264 0.884
(1.00) 		0.342
(1.00) 		0.0606
(1.00) 		0.0858
(1.00) 		0.661
(1.00)
CD3EAP 3 (1%) 266 0.857
(1.00) 		0.668
(1.00) 		1
(1.00) 		0.738
(1.00) 		1
(1.00)
F9 4 (1%) 265 0.0233
(1.00) 		0.541
(1.00) 		0.624
(1.00) 		1
(1.00)
DPP10 7 (3%) 262 0.585
(1.00) 		0.442
(1.00) 		0.261
(1.00) 		0.24
(1.00) 		1
(1.00)
TCN1 4 (1%) 265 0.907
(1.00) 		0.322
(1.00) 		0.624
(1.00) 		0.124
(1.00)
TRPV6 7 (3%) 262 0.822
(1.00) 		0.0725
(1.00) 		0.708
(1.00) 		0.825
(1.00) 		0.1
(1.00)
PAN3 6 (2%) 263 0.289
(1.00) 		0.462
(1.00) 		1
(1.00) 		0.777
(1.00) 		0.668
(1.00)
CDKN2C 3 (1%) 266 0.733
(1.00) 		0.559
(1.00) 		0.556
(1.00) 		1
(1.00)
AZGP1 4 (1%) 265 0.643
(1.00) 		0.822
(1.00) 		1
(1.00) 		1
(1.00)
DRD5 7 (3%) 262 0.63
(1.00) 		0.241
(1.00) 		1
(1.00) 		0.294
(1.00) 		1
(1.00)
FGA 6 (2%) 263 0.927
(1.00) 		0.369
(1.00) 		0.0893
(1.00) 		0.372
(1.00) 		0.668
(1.00)
FGG 5 (2%) 264 0.41
(1.00) 		0.074
(1.00) 		0.358
(1.00) 		0.294
(1.00) 		0.661
(1.00)
OR10G8 4 (1%) 265 0.877
(1.00) 		0.262
(1.00) 		0.624
(1.00) 		0.872
(1.00) 		0.613
(1.00)
PCMTD1 3 (1%) 266 0.874
(1.00) 		0.672
(1.00) 		0.556
(1.00) 		0.556
(1.00) 		0.554
(1.00)
PROKR2 6 (2%) 263 0.46
(1.00) 		0.0205
(1.00) 		1
(1.00) 		0.992
(1.00) 		0.668
(1.00)
CYP3A5 5 (2%) 264 0.349
(1.00) 		0.715
(1.00) 		0.358
(1.00) 		0.378
(1.00) 		1
(1.00)
FRMD7 6 (2%) 263 0.716
(1.00) 		0.583
(1.00) 		1
(1.00) 		0.908
(1.00) 		1
(1.00)
KCNB2 5 (2%) 264 0.357
(1.00) 		0.666
(1.00) 		0.358
(1.00) 		0.0521
(1.00)
KDR 7 (3%) 262 0.352
(1.00) 		0.775
(1.00) 		0.428
(1.00) 		0.877
(1.00) 		0.427
(1.00)
'IDH1 MUTATION STATUS' versus 'AGE'

P value = 0.000245 (t-test), Q value = 0.13

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

nPatients Mean (Std.Dev)
ALL 269 61.2 (12.6)
IDH1 MUTATED 13 41.5 (14.7)
IDH1 WILD-TYPE 256 62.2 (11.6)

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

'PRB2 MUTATION STATUS' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 0.000423 (t-test), Q value = 0.23

Table S2.  Gene #15: 'PRB2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 194 75.9 (16.0)
PRB2 MUTATED 4 80.0 (0.0)
PRB2 WILD-TYPE 190 75.8 (16.2)

Figure S2.  Get High-res Image Gene #15: 'PRB2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

'OR5W2 MUTATION STATUS' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 0.000424 (t-test), Q value = 0.23

Table S3.  Gene #38: 'OR5W2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 194 75.9 (16.0)
OR5W2 MUTATED 3 80.0 (0.0)
OR5W2 WILD-TYPE 191 75.8 (16.1)

Figure S3.  Get High-res Image Gene #38: 'OR5W2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

'OR5P2 MUTATION STATUS' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 0.000423 (t-test), Q value = 0.23

Table S4.  Gene #63: 'OR5P2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 194 75.9 (16.0)
OR5P2 MUTATED 4 80.0 (0.0)
OR5P2 WILD-TYPE 190 75.8 (16.2)

Figure S4.  Get High-res Image Gene #63: 'OR5P2 MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

'SHB MUTATION STATUS' versus 'KARNOFSKY.PERFORMANCE.SCORE'

P value = 0.000424 (t-test), Q value = 0.23

Table S5.  Gene #106: 'SHB MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

nPatients Mean (Std.Dev)
ALL 194 75.9 (16.0)
SHB MUTATED 3 80.0 (0.0)
SHB WILD-TYPE 191 75.8 (16.1)

Figure S5.  Get High-res Image Gene #106: 'SHB MUTATION STATUS' versus Clinical Feature #4: 'KARNOFSKY.PERFORMANCE.SCORE'

Methods & Data
Input

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

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

  • Number of patients = 269

  • Number of significantly mutated genes = 110

  • 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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