Correlation between gene mutation status and selected clinical features
Glioblastoma Multiforme (Primary solid tumor)
02 April 2015  |  analyses__2015_04_02
Maintainer Information
Citation Information
doi:10.7908/C1J965DV
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Cite as Broad Institute TCGA Genome Data Analysis Center (2015): Correlation between gene mutation status and selected clinical features. Broad Institute of MIT and Harvard. doi:10.7908/C1J965DV
Overview
Introduction

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

Summary

Testing the association between mutation status of 38 genes and 8 clinical features across 278 patients, 6 significant findings detected with Q value < 0.25.

  • TP53 mutation correlated to 'Time to Death'.

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

  • ATRX mutation correlated to 'YEARS_TO_BIRTH'.

  • LRRC55 mutation correlated to 'Time to Death'.

  • LZTR1 mutation correlated to 'ETHNICITY'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 38 genes and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 6 significant findings detected.

Clinical
Features 		Time
to
Death 		YEARS
TO
BIRTH 		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 14 (5%) 264 0.000454
(0.046) 		3.92e-06
(0.00119) 		0.392
(1.00) 		0.123
(1.00) 		0.494
(1.00) 		0.04
(0.752) 		0.0284
(0.663) 		1
(1.00)
TP53 78 (28%) 200 0.00179
(0.136) 		0.32
(1.00) 		0.677
(1.00) 		0.102
(1.00) 		0.351
(1.00) 		0.202
(1.00) 		0.598
(1.00) 		1
(1.00)
ATRX 16 (6%) 262 0.00713
(0.31) 		1.49e-05
(0.00226) 		0.593
(1.00) 		0.057
(0.801) 		0.546
(1.00) 		0.279
(1.00) 		0.0252
(0.663) 		1
(1.00)
LRRC55 6 (2%) 272 0.00325
(0.197) 		0.719
(1.00) 		0.67
(1.00) 		0.0955
(1.00) 		1
(1.00) 		0.667
(1.00) 		0.399
(1.00) 		1
(1.00)
LZTR1 11 (4%) 267 0.82
(1.00) 		0.446
(1.00) 		0.338
(1.00) 		0.813
(1.00) 		0.187
(1.00) 		0.514
(1.00) 		1
(1.00) 		0.00427
(0.216)
PIK3R1 32 (12%) 246 0.973
(1.00) 		0.495
(1.00) 		0.434
(1.00) 		0.76
(1.00) 		1
(1.00) 		0.69
(1.00) 		0.678
(1.00) 		1
(1.00)
RB1 23 (8%) 255 0.279
(1.00) 		0.949
(1.00) 		0.654
(1.00) 		0.0253
(0.663) 		0.681
(1.00) 		1
(1.00) 		0.602
(1.00) 		1
(1.00)
PTEN 85 (31%) 193 0.614
(1.00) 		0.324
(1.00) 		0.588
(1.00) 		0.829
(1.00) 		0.061
(0.807) 		0.678
(1.00) 		1
(1.00) 		0.227
(1.00)
NF1 29 (10%) 249 0.327
(1.00) 		0.134
(1.00) 		0.84
(1.00) 		0.241
(1.00) 		1
(1.00) 		0.54
(1.00) 		1
(1.00) 		1
(1.00)
PIK3CA 28 (10%) 250 0.195
(1.00) 		0.997
(1.00) 		0.684
(1.00) 		0.751
(1.00) 		0.498
(1.00) 		0.676
(1.00) 		0.422
(1.00) 		1
(1.00)
STAG2 12 (4%) 266 0.0114
(0.432) 		0.849
(1.00) 		0.761
(1.00) 		0.0422
(0.752) 		1
(1.00) 		0.54
(1.00) 		0.615
(1.00) 		1
(1.00)
SEMG2 11 (4%) 267 0.598
(1.00) 		0.413
(1.00) 		1
(1.00) 		0.754
(1.00) 		1
(1.00) 		0.756
(1.00) 		0.309
(1.00) 		1
(1.00)
MAP3K1 6 (2%) 272 0.657
(1.00) 		0.295
(1.00) 		0.424
(1.00) 		0.652
(1.00) 		1
(1.00) 		0.401
(1.00) 		1
(1.00) 		1
(1.00)
SLC26A3 6 (2%) 272 0.683
(1.00) 		0.279
(1.00) 		0.424
(1.00) 		0.678
(1.00) 		1
(1.00) 		0.183
(1.00) 		1
(1.00) 		1
(1.00)
BRAF 6 (2%) 272 0.242
(1.00) 		0.918
(1.00) 		1
(1.00) 		0.279
(1.00) 		0.0273
(0.663) 		0.401
(1.00) 		0.4
(1.00) 		1
(1.00)
EGFR 73 (26%) 205 0.881
(1.00) 		0.695
(1.00) 		0.257
(1.00) 		0.382
(1.00) 		0.45
(1.00) 		0.565
(1.00) 		0.413
(1.00) 		1
(1.00)
TMPRSS6 6 (2%) 272 0.978
(1.00) 		0.274
(1.00) 		0.67
(1.00) 		0.284
(1.00) 		1
(1.00) 		0.667
(1.00) 		1
(1.00) 		1
(1.00)
SEMA3C 11 (4%) 267 0.301
(1.00) 		0.995
(1.00) 		0.751
(1.00) 		0.739
(1.00) 		1
(1.00) 		0.514
(1.00) 		0.0566
(0.801) 		0.129
(1.00)
RPL5 7 (3%) 271 0.854
(1.00) 		0.803
(1.00) 		0.256
(1.00) 		0.423
(1.00) 		1
(1.00) 		0.431
(1.00) 		0.448
(1.00) 		1
(1.00)
PDGFRA 12 (4%) 266 0.737
(1.00) 		0.084
(0.946) 		1
(1.00) 		0.467
(1.00) 		1
(1.00) 		0.067
(0.815) 		1
(1.00) 		1
(1.00)
MMP13 5 (2%) 273 0.655
(1.00) 		0.12
(1.00) 		0.657
(1.00) 		0.0658
(0.815) 		1
(1.00) 		0.174
(1.00) 		1
(1.00) 		1
(1.00)
REN 5 (2%) 273 0.418
(1.00) 		0.617
(1.00) 		0.657
(1.00) 		0.333
(1.00) 		0.0791
(0.925) 		1
(1.00) 		1
(1.00) 		1
(1.00)
DSP 10 (4%) 268 0.393
(1.00) 		0.29
(1.00) 		0.75
(1.00) 		0.349
(1.00) 		1
(1.00) 		0.505
(1.00) 		1
(1.00) 		1
(1.00)
CHD8 8 (3%) 270 0.931
(1.00) 		0.0224
(0.663) 		0.141
(1.00) 		0.238
(1.00) 		1
(1.00) 		0.446
(1.00) 		1
(1.00) 		1
(1.00)
KDR 8 (3%) 270 0.645
(1.00) 		0.499
(1.00) 		0.266
(1.00) 		0.754
(1.00) 		0.32
(1.00) 		0.722
(1.00) 		1
(1.00) 		1
(1.00)
ODF4 3 (1%) 275 0.339
(1.00) 		0.568
(1.00) 		1
(1.00) 		1
(1.00) 		0.255
(1.00) 		1
(1.00) 		1
(1.00)
TP63 6 (2%) 272 0.327
(1.00) 		0.994
(1.00) 		0.67
(1.00) 		0.479
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.0531
(0.801)
PRKCD 3 (1%) 275 0.958
(1.00) 		0.123
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.224
(1.00) 		1
(1.00)
ACSM2B 4 (1%) 274 0.23
(1.00) 		0.2
(1.00) 		1
(1.00) 		0.605
(1.00) 		1
(1.00) 		0.306
(1.00) 		0.285
(1.00) 		1
(1.00)
CLCN7 4 (1%) 274 0.644
(1.00) 		0.788
(1.00) 		1
(1.00) 		0.513
(1.00) 		1
(1.00) 		0.306
(1.00) 		1
(1.00) 		1
(1.00)
DDX5 3 (1%) 275 0.0334
(0.725) 		0.0388
(0.752) 		0.555
(1.00) 		0.134
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
FBN3 11 (4%) 267 0.0944
(1.00) 		0.94
(1.00) 		0.532
(1.00) 		0.943
(1.00) 		0.189
(1.00) 		0.348
(1.00) 		0.614
(1.00) 		1
(1.00)
CD1D 4 (1%) 274 0.296
(1.00) 		0.253
(1.00) 		0.621
(1.00) 		0.706
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
TEX15 8 (3%) 270 0.15
(1.00) 		0.94
(1.00) 		0.715
(1.00) 		0.748
(1.00) 		1
(1.00) 		0.277
(1.00) 		0.495
(1.00) 		1
(1.00)
KEL 15 (5%) 263 0.805
(1.00) 		0.543
(1.00) 		0.413
(1.00) 		0.278
(1.00) 		1
(1.00) 		1
(1.00) 		0.707
(1.00) 		1
(1.00)
MUC17 21 (8%) 257 0.33
(1.00) 		0.5
(1.00) 		0.817
(1.00) 		0.782
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
SLC6A14 5 (2%) 273 0.57
(1.00) 		0.151
(1.00) 		0.354
(1.00) 		0.0445
(0.752) 		0.213
(1.00) 		0.667
(1.00) 		1
(1.00) 		1
(1.00)
CD209 5 (2%) 273 0.697
(1.00) 		0.717
(1.00) 		0.0579
(0.801) 		0.605
(1.00) 		1
(1.00) 		0.667
(1.00) 		1
(1.00) 		1
(1.00)
'TP53 MUTATION STATUS' versus 'Time to Death'

P value = 0.00179 (logrank test), Q value = 0.14

Table S1.  Gene #1: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 278 211 0.1 - 120.6 (10.8)
TP53 MUTATED 78 50 0.4 - 69.9 (12.1)
TP53 WILD-TYPE 200 161 0.1 - 120.6 (10.5)

Figure S1.  Get High-res Image Gene #1: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'IDH1 MUTATION STATUS' versus 'Time to Death'

P value = 0.000454 (logrank test), Q value = 0.046

Table S2.  Gene #6: 'IDH1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 278 211 0.1 - 120.6 (10.8)
IDH1 MUTATED 14 4 3.4 - 50.5 (21.9)
IDH1 WILD-TYPE 264 207 0.1 - 120.6 (10.7)

Figure S2.  Get High-res Image Gene #6: 'IDH1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'IDH1 MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 3.92e-06 (Wilcoxon-test), Q value = 0.0012

Table S3.  Gene #6: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 278 61.0 (13.0)
IDH1 MUTATED 14 40.0 (15.1)
IDH1 WILD-TYPE 264 62.2 (11.9)

Figure S3.  Get High-res Image Gene #6: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'ATRX MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 1.49e-05 (Wilcoxon-test), Q value = 0.0023

Table S4.  Gene #12: 'ATRX MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 278 61.0 (13.0)
ATRX MUTATED 16 42.7 (16.4)
ATRX WILD-TYPE 262 62.2 (11.9)

Figure S4.  Get High-res Image Gene #12: 'ATRX MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'LRRC55 MUTATION STATUS' versus 'Time to Death'

P value = 0.00325 (logrank test), Q value = 0.2

Table S5.  Gene #36: 'LRRC55 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 278 211 0.1 - 120.6 (10.8)
LRRC55 MUTATED 6 2 9.0 - 73.8 (33.8)
LRRC55 WILD-TYPE 272 209 0.1 - 120.6 (10.7)

Figure S5.  Get High-res Image Gene #36: 'LRRC55 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'LZTR1 MUTATION STATUS' versus 'ETHNICITY'

P value = 0.00427 (Fisher's exact test), Q value = 0.22

Table S6.  Gene #38: 'LZTR1 MUTATION STATUS' versus Clinical Feature #8: 'ETHNICITY'

nPatients HISPANIC OR LATINO NOT HISPANIC OR LATINO
ALL 3 220
LZTR1 MUTATED 2 7
LZTR1 WILD-TYPE 1 213

Figure S6.  Get High-res Image Gene #38: 'LZTR1 MUTATION STATUS' versus Clinical Feature #8: 'ETHNICITY'

Methods & Data
Input

  • Mutation data file = sample_sig_gene_table.txt from Mutsig_2CV pipeline

  • Processed Mutation data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/GDAC_Correlate_Genomic_Events_Preprocess/GBM-TP/15658343/transformed.cor.cli.txt

  • Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/GBM-TP/15078636/GBM-TP.merged_data.txt

  • Number of patients = 278

  • Number of significantly mutated genes = 38

  • 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)
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