Correlation between gene mutation status and selected clinical features
Brain Lower Grade Glioma (Primary solid tumor)
15 July 2014  |  analyses__2014_07_15
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 (2014): Correlation between gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C17S7MJF
Overview
Introduction

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

Summary

Testing the association between mutation status of 36 genes and 8 clinical features across 282 patients, 15 significant findings detected with Q value < 0.25.

  • IDH1 mutation correlated to 'Time to Death' and 'AGE'.

  • TP53 mutation correlated to 'AGE' and 'HISTOLOGICAL.TYPE'.

  • ATRX mutation correlated to 'AGE' and 'HISTOLOGICAL.TYPE'.

  • CIC mutation correlated to 'HISTOLOGICAL.TYPE'.

  • NOTCH1 mutation correlated to 'HISTOLOGICAL.TYPE'.

  • FUBP1 mutation correlated to 'HISTOLOGICAL.TYPE'.

  • NF1 mutation correlated to 'Time to Death'.

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

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

  • PLCG1 mutation correlated to 'Time to Death'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 36 genes and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 15 significant findings detected.

Clinical
Features
Time
to
Death
AGE GENDER KARNOFSKY
PERFORMANCE
SCORE
HISTOLOGICAL
TYPE
RADIATIONS
RADIATION
REGIMENINDICATION
RACE ETHNICITY
nMutated (%) nWild-Type logrank test Wilcoxon-test Fisher's exact test Wilcoxon-test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
IDH1 215 (76%) 67 4.7e-09
(1.3e-06)
0.000464
(0.124)
0.124
(1.00)
0.0372
(1.00)
0.0262
(1.00)
0.762
(1.00)
0.178
(1.00)
0.328
(1.00)
TP53 143 (51%) 139 0.36
(1.00)
7.58e-07
(0.000207)
0.119
(1.00)
0.197
(1.00)
1e-05
(0.00271)
0.0271
(1.00)
0.469
(1.00)
1
(1.00)
ATRX 116 (41%) 166 0.0889
(1.00)
1.26e-07
(3.46e-05)
0.226
(1.00)
0.0972
(1.00)
1e-05
(0.00271)
0.0666
(1.00)
0.746
(1.00)
1
(1.00)
PTEN 13 (5%) 269 3.79e-08
(1.05e-05)
0.000737
(0.195)
0.571
(1.00)
0.106
(1.00)
0.00537
(1.00)
0.541
(1.00)
0.144
(1.00)
1
(1.00)
EGFR 16 (6%) 266 0
(0)
2.11e-07
(5.78e-05)
0.616
(1.00)
0.00179
(0.467)
0.299
(1.00)
0.161
(1.00)
0.545
(1.00)
1
(1.00)
CIC 53 (19%) 229 0.0528
(1.00)
0.337
(1.00)
0.284
(1.00)
0.494
(1.00)
1e-05
(0.00271)
0.134
(1.00)
0.757
(1.00)
1
(1.00)
NOTCH1 28 (10%) 254 0.743
(1.00)
0.0411
(1.00)
1
(1.00)
0.561
(1.00)
2e-05
(0.00536)
0.386
(1.00)
0.656
(1.00)
1
(1.00)
FUBP1 26 (9%) 256 0.95
(1.00)
0.00443
(1.00)
1
(1.00)
0.638
(1.00)
2e-05
(0.00536)
1
(1.00)
1
(1.00)
0.619
(1.00)
NF1 19 (7%) 263 0.000493
(0.131)
0.194
(1.00)
0.813
(1.00)
0.339
(1.00)
0.0797
(1.00)
0.119
(1.00)
0.25
(1.00)
0.265
(1.00)
PLCG1 4 (1%) 278 1.07e-06
(0.000291)
0.0604
(1.00)
1
(1.00)
0.656
(1.00)
0.683
(1.00)
0.586
(1.00)
0.177
(1.00)
1
(1.00)
IDH2 12 (4%) 270 0.252
(1.00)
0.237
(1.00)
0.77
(1.00)
0.911
(1.00)
0.00999
(1.00)
0.757
(1.00)
0.442
(1.00)
0.109
(1.00)
PIK3R1 13 (5%) 269 0.537
(1.00)
0.136
(1.00)
0.156
(1.00)
0.493
(1.00)
0.247
(1.00)
0.221
(1.00)
0.444
(1.00)
1
(1.00)
STK19 6 (2%) 276 0.0718
(1.00)
0.915
(1.00)
0.41
(1.00)
0.074
(1.00)
0.25
(1.00)
0.183
(1.00)
1
(1.00)
0.0345
(1.00)
PIK3CA 25 (9%) 257 0.0757
(1.00)
0.118
(1.00)
0.833
(1.00)
0.394
(1.00)
0.0433
(1.00)
0.649
(1.00)
1
(1.00)
1
(1.00)
ARID1A 12 (4%) 270 0.123
(1.00)
0.882
(1.00)
0.0143
(1.00)
0.0415
(1.00)
0.344
(1.00)
1
(1.00)
1
(1.00)
0.486
(1.00)
GAGE2B 4 (1%) 278 0.805
(1.00)
0.8
(1.00)
0.633
(1.00)
1
(1.00)
1
(1.00)
1
(1.00)
0.196
(1.00)
CREBZF 5 (2%) 277 0.754
(1.00)
0.246
(1.00)
0.173
(1.00)
0.175
(1.00)
0.224
(1.00)
1
(1.00)
0.215
(1.00)
1
(1.00)
TCF12 8 (3%) 274 0.314
(1.00)
0.0886
(1.00)
0.734
(1.00)
0.44
(1.00)
0.179
(1.00)
0.442
(1.00)
1
(1.00)
1
(1.00)
SMARCA4 13 (5%) 269 0.106
(1.00)
0.145
(1.00)
0.78
(1.00)
0.038
(1.00)
0.516
(1.00)
0.0677
(1.00)
1
(1.00)
0.486
(1.00)
VAV3 8 (3%) 274 0.426
(1.00)
0.902
(1.00)
0.306
(1.00)
0.00128
(0.335)
0.74
(1.00)
0.701
(1.00)
1
(1.00)
0.356
(1.00)
ROBO3 3 (1%) 279 0.724
(1.00)
0.974
(1.00)
0.584
(1.00)
0.782
(1.00)
1
(1.00)
1
(1.00)
1
(1.00)
IRS4 5 (2%) 277 0.682
(1.00)
0.98
(1.00)
1
(1.00)
0.197
(1.00)
0.38
(1.00)
1
(1.00)
1
(1.00)
0.239
(1.00)
HTRA2 4 (1%) 278 0.848
(1.00)
0.0732
(1.00)
0.633
(1.00)
0.566
(1.00)
0.319
(1.00)
1
(1.00)
0.196
(1.00)
EIF1AX 4 (1%) 278 0.38
(1.00)
0.988
(1.00)
0.133
(1.00)
0.911
(1.00)
0.186
(1.00)
0.586
(1.00)
1
(1.00)
1
(1.00)
FAM47C 7 (2%) 275 0.175
(1.00)
0.953
(1.00)
1
(1.00)
0.548
(1.00)
0.0714
(1.00)
1
(1.00)
1
(1.00)
0.319
(1.00)
DDX5 4 (1%) 278 0.577
(1.00)
0.894
(1.00)
0.633
(1.00)
0.305
(1.00)
0.68
(1.00)
1
(1.00)
1
(1.00)
0.151
(1.00)
ZNF709 3 (1%) 279 0.566
(1.00)
0.584
(1.00)
0.258
(1.00)
0.495
(1.00)
0.217
(1.00)
0.134
(1.00)
1
(1.00)
TRERF1 3 (1%) 279 0.731
(1.00)
0.698
(1.00)
0.0839
(1.00)
0.364
(1.00)
0.556
(1.00)
1
(1.00)
1
(1.00)
BCOR 9 (3%) 273 0.958
(1.00)
0.167
(1.00)
0.046
(1.00)
0.302
(1.00)
0.48
(1.00)
1
(1.00)
0.355
(1.00)
1
(1.00)
SRPX 3 (1%) 279 0.473
(1.00)
0.109
(1.00)
0.0839
(1.00)
0.784
(1.00)
1
(1.00)
1
(1.00)
1
(1.00)
DOCK5 5 (2%) 277 0.00625
(1.00)
0.0226
(1.00)
1
(1.00)
0.724
(1.00)
1
(1.00)
0.639
(1.00)
1
(1.00)
1
(1.00)
GIGYF2 4 (1%) 278 0.00116
(0.305)
0.734
(1.00)
1
(1.00)
0.829
(1.00)
0.0833
(1.00)
1
(1.00)
1
(1.00)
NIPBL 5 (2%) 277 0.091
(1.00)
0.0284
(1.00)
0.389
(1.00)
0.185
(1.00)
1
(1.00)
1
(1.00)
0.239
(1.00)
ZBTB20 13 (5%) 269 0.405
(1.00)
0.643
(1.00)
0.4
(1.00)
0.95
(1.00)
0.395
(1.00)
0.118
(1.00)
0.144
(1.00)
0.486
(1.00)
TRIP12 5 (2%) 277 0.218
(1.00)
0.64
(1.00)
1
(1.00)
0.153
(1.00)
0.163
(1.00)
1
(1.00)
1
(1.00)
KIAA0664 5 (2%) 277 0.995
(1.00)
0.96
(1.00)
1
(1.00)
0.223
(1.00)
0.163
(1.00)
1
(1.00)
1
(1.00)
'IDH1 MUTATION STATUS' versus 'Time to Death'

P value = 4.7e-09 (logrank test), Q value = 1.3e-06

Table S1.  Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 280 57 0.0 - 182.3 (15.0)
IDH1 MUTATED 213 32 0.0 - 182.3 (15.5)
IDH1 WILD-TYPE 67 25 0.1 - 133.7 (11.6)

Figure S1.  Get High-res Image Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'IDH1 MUTATION STATUS' versus 'AGE'

P value = 0.000464 (Wilcoxon-test), Q value = 0.12

Table S2.  Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 282 42.7 (13.5)
IDH1 MUTATED 215 41.0 (12.7)
IDH1 WILD-TYPE 67 48.2 (14.6)

Figure S2.  Get High-res Image Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'TP53 MUTATION STATUS' versus 'AGE'

P value = 7.58e-07 (Wilcoxon-test), Q value = 0.00021

Table S3.  Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 282 42.7 (13.5)
TP53 MUTATED 143 38.7 (11.8)
TP53 WILD-TYPE 139 46.8 (13.9)

Figure S3.  Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'TP53 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.0027

Table S4.  Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 94 76 112
TP53 MUTATED 64 50 29
TP53 WILD-TYPE 30 26 83

Figure S4.  Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'ATRX MUTATION STATUS' versus 'AGE'

P value = 1.26e-07 (Wilcoxon-test), Q value = 3.5e-05

Table S5.  Gene #3: 'ATRX MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 282 42.7 (13.5)
ATRX MUTATED 116 37.6 (11.5)
ATRX WILD-TYPE 166 46.3 (13.6)

Figure S5.  Get High-res Image Gene #3: 'ATRX MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'ATRX MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.0027

Table S6.  Gene #3: 'ATRX MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 94 76 112
ATRX MUTATED 47 43 26
ATRX WILD-TYPE 47 33 86

Figure S6.  Get High-res Image Gene #3: 'ATRX MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'CIC MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.0027

Table S7.  Gene #4: 'CIC MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 94 76 112
CIC MUTATED 1 9 43
CIC WILD-TYPE 93 67 69

Figure S7.  Get High-res Image Gene #4: 'CIC MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'NOTCH1 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 2e-05 (Fisher's exact test), Q value = 0.0054

Table S8.  Gene #5: 'NOTCH1 MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 94 76 112
NOTCH1 MUTATED 2 3 23
NOTCH1 WILD-TYPE 92 73 89

Figure S8.  Get High-res Image Gene #5: 'NOTCH1 MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'FUBP1 MUTATION STATUS' versus 'HISTOLOGICAL.TYPE'

P value = 2e-05 (Fisher's exact test), Q value = 0.0054

Table S9.  Gene #7: 'FUBP1 MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 94 76 112
FUBP1 MUTATED 1 3 22
FUBP1 WILD-TYPE 93 73 90

Figure S9.  Get High-res Image Gene #7: 'FUBP1 MUTATION STATUS' versus Clinical Feature #5: 'HISTOLOGICAL.TYPE'

'NF1 MUTATION STATUS' versus 'Time to Death'

P value = 0.000493 (logrank test), Q value = 0.13

Table S10.  Gene #8: 'NF1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 280 57 0.0 - 182.3 (15.0)
NF1 MUTATED 19 8 0.2 - 73.0 (18.0)
NF1 WILD-TYPE 261 49 0.0 - 182.3 (14.9)

Figure S10.  Get High-res Image Gene #8: 'NF1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'PTEN MUTATION STATUS' versus 'Time to Death'

P value = 3.79e-08 (logrank test), Q value = 1e-05

Table S11.  Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 280 57 0.0 - 182.3 (15.0)
PTEN MUTATED 13 6 0.5 - 21.0 (10.4)
PTEN WILD-TYPE 267 51 0.0 - 182.3 (15.2)

Figure S11.  Get High-res Image Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'PTEN MUTATION STATUS' versus 'AGE'

P value = 0.000737 (Wilcoxon-test), Q value = 0.19

Table S12.  Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 282 42.7 (13.5)
PTEN MUTATED 13 55.3 (10.5)
PTEN WILD-TYPE 269 42.1 (13.3)

Figure S12.  Get High-res Image Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'EGFR MUTATION STATUS' versus 'Time to Death'

P value = 0 (logrank test), Q value = 0

Table S13.  Gene #14: 'EGFR MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 280 57 0.0 - 182.3 (15.0)
EGFR MUTATED 16 8 0.5 - 13.6 (5.9)
EGFR WILD-TYPE 264 49 0.0 - 182.3 (15.6)

Figure S13.  Get High-res Image Gene #14: 'EGFR MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'EGFR MUTATION STATUS' versus 'AGE'

P value = 2.11e-07 (Wilcoxon-test), Q value = 5.8e-05

Table S14.  Gene #14: 'EGFR MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 282 42.7 (13.5)
EGFR MUTATED 16 61.1 (7.3)
EGFR WILD-TYPE 266 41.6 (13.0)

Figure S14.  Get High-res Image Gene #14: 'EGFR MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'PLCG1 MUTATION STATUS' versus 'Time to Death'

P value = 1.07e-06 (logrank test), Q value = 0.00029

Table S15.  Gene #25: 'PLCG1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 280 57 0.0 - 182.3 (15.0)
PLCG1 MUTATED 4 3 6.7 - 21.0 (7.2)
PLCG1 WILD-TYPE 276 54 0.0 - 182.3 (15.0)

Figure S15.  Get High-res Image Gene #25: 'PLCG1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

Methods & Data
Input
  • Mutation data file = transformed.cor.cli.txt

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

  • Number of patients = 282

  • Number of significantly mutated genes = 36

  • Number of selected clinical features = 8

  • 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

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] 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)
[3] 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)