Correlation between gene mutation status and selected clinical features
Adrenocortical Carcinoma (Primary solid tumor)
16 April 2014  |  analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1D7990B
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 gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1D7990B
Overview
Introduction

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

Summary

Testing the association between mutation status of 97 genes and 6 clinical features across 34 patients, 3 significant findings detected with Q value < 0.25.

  • SCRT1 mutation correlated to 'Time to Death' and 'AGE'.

  • MADCAM1 mutation correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 97 genes and 6 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 3 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE NEOPLASM
DISEASESTAGE 		PATHOLOGY
T
STAGE 		PATHOLOGY
N
STAGE 		GENDER
nMutated (%) nWild-Type logrank test t-test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
SCRT1 4 (12%) 30 1.68e-05
(0.00935) 		0.000254
(0.141) 		0.693
(1.00) 		0.788
(1.00) 		0.075
(1.00) 		1
(1.00)
MADCAM1 3 (9%) 31 0.0045
(1.00) 		5.59e-05
(0.031) 		0.161
(1.00) 		0.0389
(1.00) 		0.0394
(1.00) 		1
(1.00)
NMU 7 (21%) 27 0.953
(1.00) 		0.258
(1.00) 		0.502
(1.00) 		0.83
(1.00) 		0.0181
(1.00) 		0.398
(1.00)
LPPR2 3 (9%) 31 0.0026
(1.00) 		0.726
(1.00) 		0.253
(1.00) 		1
(1.00)
SYT8 6 (18%) 28 0.648
(1.00) 		0.27
(1.00) 		0.916
(1.00) 		1
(1.00) 		1
(1.00) 		0.175
(1.00)
RINL 8 (24%) 26 0.661
(1.00) 		0.516
(1.00) 		0.859
(1.00) 		0.51
(1.00) 		1
(1.00) 		0.688
(1.00)
OBSCN 15 (44%) 19 0.382
(1.00) 		0.0591
(1.00) 		0.748
(1.00) 		0.592
(1.00) 		1
(1.00) 		1
(1.00)
MAP1S 4 (12%) 30 0.28
(1.00) 		0.161
(1.00) 		0.693
(1.00) 		1
(1.00) 		0.454
(1.00) 		1
(1.00)
GPRIN2 4 (12%) 30 0.884
(1.00) 		0.907
(1.00) 		0.356
(1.00) 		1
(1.00) 		1
(1.00) 		0.601
(1.00)
ATP9B 3 (9%) 31 0.328
(1.00) 		0.121
(1.00) 		0.253
(1.00) 		1
(1.00)
RREB1 4 (12%) 30 0.954
(1.00) 		0.166
(1.00) 		1
(1.00) 		1
(1.00) 		0.454
(1.00) 		1
(1.00)
IDUA 6 (18%) 28 0.636
(1.00) 		0.727
(1.00) 		0.79
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
RGS9BP 6 (18%) 28 0.791
(1.00) 		0.103
(1.00) 		0.0884
(1.00) 		0.327
(1.00) 		1
(1.00) 		0.656
(1.00)
WDR34 4 (12%) 30 0.759
(1.00) 		0.0642
(1.00) 		0.602
(1.00) 		0.704
(1.00) 		0.36
(1.00) 		0.601
(1.00)
NOTCH2 3 (9%) 31 0.32
(1.00) 		0.968
(1.00) 		0.133
(1.00) 		1
(1.00)
TMEM189 3 (9%) 31 0.337
(1.00) 		0.244
(1.00) 		1
(1.00) 		1
(1.00)
TAF5 5 (15%) 29 0.383
(1.00) 		0.455
(1.00) 		0.693
(1.00) 		0.788
(1.00) 		0.454
(1.00) 		0.335
(1.00)
LRP11 4 (12%) 30 0.312
(1.00) 		0.724
(1.00) 		1
(1.00) 		0.601
(1.00)
FPGS 7 (21%) 27 0.314
(1.00) 		0.024
(1.00) 		0.923
(1.00) 		0.83
(1.00) 		0.225
(1.00) 		1
(1.00)
TOR3A 13 (38%) 21 0.304
(1.00) 		0.947
(1.00) 		0.108
(1.00) 		0.0979
(1.00) 		0.611
(1.00) 		0.481
(1.00)
ZNF517 17 (50%) 17 0.493
(1.00) 		0.267
(1.00) 		0.792
(1.00) 		0.679
(1.00) 		0.598
(1.00) 		0.494
(1.00)
GLTPD2 10 (29%) 24 0.608
(1.00) 		0.235
(1.00) 		0.674
(1.00) 		1
(1.00) 		1
(1.00) 		0.708
(1.00)
SEMA5B 7 (21%) 27 0.597
(1.00) 		0.446
(1.00) 		0.492
(1.00) 		0.412
(1.00) 		1
(1.00) 		1
(1.00)
TNIP2 3 (9%) 31 0.287
(1.00) 		0.774
(1.00) 		1
(1.00) 		1
(1.00)
HHIPL1 5 (15%) 29 0.909
(1.00) 		0.968
(1.00) 		0.312
(1.00) 		0.66
(1.00) 		0.119
(1.00) 		1
(1.00)
HECTD2 3 (9%) 31 0.0118
(1.00) 		0.337
(1.00) 		0.829
(1.00) 		0.704
(1.00) 		1
(1.00) 		0.227
(1.00)
ADAD2 10 (29%) 24 0.164
(1.00) 		0.742
(1.00) 		0.343
(1.00) 		0.853
(1.00) 		0.563
(1.00) 		1
(1.00)
CTNNB1 7 (21%) 27 0.00515
(1.00) 		0.239
(1.00) 		0.712
(1.00) 		0.51
(1.00) 		0.225
(1.00) 		0.0854
(1.00)
ZFPM1 19 (56%) 15 0.0784
(1.00) 		0.828
(1.00) 		0.0224
(1.00) 		0.448
(1.00) 		0.613
(1.00) 		1
(1.00)
CLDN23 4 (12%) 30 0.996
(1.00) 		0.39
(1.00) 		0.531
(1.00) 		0.424
(1.00) 		0.454
(1.00) 		1
(1.00)
CCDC105 4 (12%) 30 0.571
(1.00) 		0.581
(1.00) 		0.356
(1.00) 		0.327
(1.00) 		1
(1.00) 		0.103
(1.00)
NOL9 7 (21%) 27 0.998
(1.00) 		0.00558
(1.00) 		0.244
(1.00) 		0.37
(1.00) 		1
(1.00) 		1
(1.00)
ZNF598 7 (21%) 27 0.554
(1.00) 		0.0053
(1.00) 		0.0475
(1.00) 		0.0439
(1.00) 		0.557
(1.00) 		1
(1.00)
THEM4 6 (18%) 28 0.08
(1.00) 		0.827
(1.00) 		1
(1.00) 		0.788
(1.00) 		0.454
(1.00) 		0.656
(1.00)
LRIG1 16 (47%) 18 0.0659
(1.00) 		0.997
(1.00) 		0.593
(1.00) 		0.194
(1.00) 		1
(1.00) 		0.303
(1.00)
MUC5B 8 (24%) 26 0.549
(1.00) 		0.412
(1.00) 		0.715
(1.00) 		0.83
(1.00) 		0.557
(1.00) 		0.688
(1.00)
AMDHD1 10 (29%) 24 0.937
(1.00) 		0.345
(1.00) 		0.663
(1.00) 		1
(1.00) 		1
(1.00) 		0.708
(1.00)
RNF149 3 (9%) 31 0.37
(1.00) 		0.609
(1.00) 		0.0996
(1.00) 		0.0651
(1.00) 		1
(1.00) 		0.227
(1.00)
MSH3 3 (9%) 31 0.0326
(1.00) 		0.917
(1.00) 		0.161
(1.00) 		0.105
(1.00) 		0.36
(1.00) 		1
(1.00)
ALPPL2 3 (9%) 31 0.328
(1.00) 		0.828
(1.00) 		0.829
(1.00) 		0.704
(1.00) 		1
(1.00) 		1
(1.00)
SNED1 4 (12%) 30 0.195
(1.00) 		0.704
(1.00) 		0.531
(1.00) 		0.424
(1.00) 		0.075
(1.00) 		1
(1.00)
OPRD1 11 (32%) 23 0.971
(1.00) 		0.652
(1.00) 		0.878
(1.00) 		0.738
(1.00) 		1
(1.00) 		0.0255
(1.00)
CCDC102A 11 (32%) 23 0.217
(1.00) 		0.121
(1.00) 		0.0298
(1.00) 		0.0751
(1.00) 		0.272
(1.00) 		1
(1.00)
KCTD3 4 (12%) 30 0.438
(1.00) 		0.681
(1.00) 		0.829
(1.00) 		0.704
(1.00) 		0.36
(1.00) 		1
(1.00)
C1ORF106 6 (18%) 28 0.728
(1.00) 		0.98
(1.00) 		0.406
(1.00) 		0.288
(1.00) 		1
(1.00) 		0.175
(1.00)
KCNK17 9 (26%) 25 0.176
(1.00) 		0.672
(1.00) 		0.738
(1.00) 		1
(1.00) 		0.284
(1.00) 		0.438
(1.00)
LACTB 11 (32%) 23 0.79
(1.00) 		0.284
(1.00) 		0.0852
(1.00) 		0.233
(1.00) 		0.272
(1.00) 		1
(1.00)
TRIOBP 9 (26%) 25 0.929
(1.00) 		0.594
(1.00) 		0.532
(1.00) 		0.213
(1.00) 		1
(1.00) 		1
(1.00)
SARM1 5 (15%) 29 0.438
(1.00) 		0.439
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
ERCC2 11 (32%) 23 0.185
(1.00) 		0.835
(1.00) 		0.942
(1.00) 		1
(1.00) 		0.611
(1.00) 		0.465
(1.00)
NEFH 4 (12%) 30 0.987
(1.00) 		0.848
(1.00) 		0.531
(1.00) 		0.788
(1.00) 		0.075
(1.00) 		1
(1.00)
KBTBD13 8 (24%) 26 0.482
(1.00) 		0.271
(1.00) 		0.663
(1.00) 		0.534
(1.00) 		0.284
(1.00) 		0.688
(1.00)
IRX3 9 (26%) 25 0.361
(1.00) 		0.809
(1.00) 		0.216
(1.00) 		0.619
(1.00) 		1
(1.00) 		0.118
(1.00)
MUC2 7 (21%) 27 0.243
(1.00) 		0.133
(1.00) 		0.058
(1.00) 		0.0271
(1.00) 		0.557
(1.00) 		0.0854
(1.00)
GARS 14 (41%) 20 0.459
(1.00) 		0.443
(1.00) 		0.116
(1.00) 		0.436
(1.00) 		0.613
(1.00) 		0.728
(1.00)
UQCRFS1 7 (21%) 27 0.702
(1.00) 		0.907
(1.00) 		0.492
(1.00) 		0.412
(1.00) 		0.225
(1.00) 		1
(1.00)
ZNF628 5 (15%) 29 0.00972
(1.00) 		0.747
(1.00) 		0.762
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
ASPDH 11 (32%) 23 0.653
(1.00) 		0.724
(1.00) 		0.284
(1.00) 		0.644
(1.00) 		1
(1.00) 		0.465
(1.00)
TPO 10 (29%) 24 0.916
(1.00) 		0.772
(1.00) 		0.198
(1.00) 		0.339
(1.00) 		0.287
(1.00) 		0.259
(1.00)
GLTSCR2 4 (12%) 30 0.453
(1.00) 		0.35
(1.00) 		0.693
(1.00) 		0.788
(1.00) 		1
(1.00) 		0.601
(1.00)
PANK2 7 (21%) 27 0.833
(1.00) 		0.9
(1.00) 		0.849
(1.00) 		0.83
(1.00) 		0.169
(1.00) 		0.398
(1.00)
RNF39 3 (9%) 31 0.0782
(1.00) 		0.069
(1.00) 		0.253
(1.00) 		1
(1.00)
MAL2 7 (21%) 27 0.957
(1.00) 		0.0128
(1.00) 		0.431
(1.00) 		0.024
(1.00) 		1
(1.00) 		0.398
(1.00)
ZAR1 11 (32%) 23 0.168
(1.00) 		0.924
(1.00) 		0.25
(1.00) 		0.358
(1.00) 		1
(1.00) 		0.141
(1.00)
KRTAP5-5 3 (9%) 31 0.0118
(1.00) 		0.337
(1.00) 		0.829
(1.00) 		0.704
(1.00) 		1
(1.00) 		0.227
(1.00)
CRIPAK 6 (18%) 28 0.371
(1.00) 		0.179
(1.00) 		0.715
(1.00) 		0.83
(1.00) 		1
(1.00) 		0.656
(1.00)
TP53 7 (21%) 27 0.0283
(1.00) 		0.18
(1.00) 		0.015
(1.00) 		0.00258
(1.00) 		0.169
(1.00) 		1
(1.00)
BHLHE22 4 (12%) 30 0.381
(1.00) 		0.985
(1.00) 		1
(1.00) 		0.788
(1.00) 		0.454
(1.00) 		1
(1.00)
RGMB 3 (9%) 31 0.578
(1.00) 		0.932
(1.00) 		0.829
(1.00) 		0.704
(1.00) 		0.36
(1.00) 		1
(1.00)
APOE 6 (18%) 28 0.597
(1.00) 		0.175
(1.00) 		0.916
(1.00) 		1
(1.00) 		1
(1.00) 		0.656
(1.00)
MEN1 3 (9%) 31 0.91
(1.00) 		0.121
(1.00) 		1
(1.00) 		1
(1.00)
RASIP1 4 (12%) 30 0.306
(1.00) 		0.445
(1.00) 		1
(1.00) 		0.788
(1.00) 		0.454
(1.00) 		0.601
(1.00)
ZC3H12D 3 (9%) 31 0.113
(1.00) 		0.222
(1.00) 		1
(1.00) 		1
(1.00)
TSC22D2 7 (21%) 27 0.118
(1.00) 		0.85
(1.00) 		0.312
(1.00) 		0.0368
(1.00) 		0.169
(1.00) 		1
(1.00)
COQ2 5 (15%) 29 0.791
(1.00) 		0.306
(1.00) 		0.916
(1.00) 		1
(1.00) 		1
(1.00) 		0.335
(1.00)
DOK7 5 (15%) 29 0.204
(1.00) 		0.564
(1.00) 		0.147
(1.00) 		0.0631
(1.00) 		1
(1.00) 		1
(1.00)
KNDC1 7 (21%) 27 0.251
(1.00) 		0.497
(1.00) 		0.406
(1.00) 		0.288
(1.00) 		1
(1.00) 		1
(1.00)
PDCD6 3 (9%) 31 0.744
(1.00) 		0.661
(1.00) 		0.0416
(1.00) 		0.0159
(1.00) 		0.36
(1.00) 		1
(1.00)
ATP6V0E2 4 (12%) 30 0.289
(1.00) 		0.048
(1.00) 		0.502
(1.00) 		0.389
(1.00) 		1
(1.00) 		0.601
(1.00)
HES3 3 (9%) 31 0.385
(1.00) 		0.198
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
PRKAR1A 3 (9%) 31 0.0583
(1.00) 		0.877
(1.00) 		0.161
(1.00) 		0.105
(1.00) 		0.36
(1.00) 		0.227
(1.00)
ATOH8 3 (9%) 31 0.188
(1.00) 		0.99
(1.00) 		0.829
(1.00) 		0.704
(1.00) 		0.36
(1.00) 		1
(1.00)
BTBD11 4 (12%) 30 0.055
(1.00) 		0.646
(1.00) 		0.602
(1.00) 		0.424
(1.00) 		0.454
(1.00) 		1
(1.00)
PLIN5 4 (12%) 30 0.704
(1.00) 		0.283
(1.00) 		0.79
(1.00) 		1
(1.00) 		0.454
(1.00) 		1
(1.00)
ASB16 4 (12%) 30 0.867
(1.00) 		0.488
(1.00) 		1
(1.00) 		0.788
(1.00) 		1
(1.00) 		0.601
(1.00)
NPTX1 5 (15%) 29 0.237
(1.00) 		0.101
(1.00) 		0.147
(1.00) 		0.0631
(1.00) 		1
(1.00) 		1
(1.00)
LRRN4 3 (9%) 31 0.438
(1.00) 		0.397
(1.00) 		0.602
(1.00) 		1
(1.00) 		0.36
(1.00) 		1
(1.00)
CCDC96 4 (12%) 30 0.337
(1.00) 		0.136
(1.00) 		0.829
(1.00) 		0.704
(1.00) 		0.36
(1.00) 		0.601
(1.00)
PCMTD1 3 (9%) 31 0.851
(1.00) 		0.439
(1.00) 		1
(1.00) 		1
(1.00)
GLI3 5 (15%) 29 0.769
(1.00) 		0.0234
(1.00) 		0.602
(1.00) 		0.424
(1.00) 		1
(1.00) 		1
(1.00)
MN1 3 (9%) 31 0.138
(1.00) 		0.0816
(1.00) 		1
(1.00) 		0.389
(1.00) 		0.36
(1.00) 		0.227
(1.00)
C9ORF66 3 (9%) 31 0.834
(1.00) 		0.365
(1.00) 		0.502
(1.00) 		0.236
(1.00) 		1
(1.00) 		1
(1.00)
KRTAP10-7 3 (9%) 31 0.289
(1.00) 		0.765
(1.00) 		1
(1.00) 		1
(1.00)
ARRDC4 5 (15%) 29 0.652
(1.00) 		0.58
(1.00) 		0.916
(1.00) 		1
(1.00) 		0.538
(1.00) 		1
(1.00)
VARS 3 (9%) 31 0.254
(1.00) 		0.274
(1.00) 		1
(1.00) 		1
(1.00)
PLEC 6 (18%) 28 0.204
(1.00) 		0.387
(1.00) 		0.469
(1.00) 		1
(1.00) 		0.557
(1.00) 		0.656
(1.00)
RCCD1 3 (9%) 31 0.348
(1.00) 		0.605
(1.00) 		1
(1.00) 		1
(1.00)
'SCRT1 MUTATION STATUS' versus 'Time to Death'

P value = 1.68e-05 (logrank test), Q value = 0.0094

Table S1.  Gene #84: 'SCRT1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 34 8 6.9 - 121.2 (29.8)
SCRT1 MUTATED 4 2 6.9 - 18.1 (10.7)
SCRT1 WILD-TYPE 30 6 8.3 - 121.2 (32.0)

Figure S1.  Get High-res Image Gene #84: 'SCRT1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'SCRT1 MUTATION STATUS' versus 'AGE'

P value = 0.000254 (t-test), Q value = 0.14

Table S2.  Gene #84: 'SCRT1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 34 50.8 (14.3)
SCRT1 MUTATED 4 63.5 (3.7)
SCRT1 WILD-TYPE 30 49.1 (14.4)

Figure S2.  Get High-res Image Gene #84: 'SCRT1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'MADCAM1 MUTATION STATUS' versus 'AGE'

P value = 5.59e-05 (t-test), Q value = 0.031

Table S3.  Gene #92: 'MADCAM1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 34 50.8 (14.3)
MADCAM1 MUTATED 3 63.3 (2.1)
MADCAM1 WILD-TYPE 31 49.6 (14.4)

Figure S3.  Get High-res Image Gene #92: 'MADCAM1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

  • Mutation data file = transformed.cor.cli.txt

  • Clinical data file = ACC-TP.merged_data.txt

  • Number of patients = 34

  • Number of significantly mutated genes = 97

  • 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

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] 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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