Correlation between gene mutation status and selected clinical features
Overview
Introduction

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

Summary

Testing the association between mutation status of 59 genes and 8 clinical features across 130 patients, 3 significant findings detected with Q value < 0.25.

  • CHD4 mutation correlated to 'Time to Death' and 'RACE'.

  • PIK3CD mutation correlated to 'Time to Death'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 59 genes and 8 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 		YEARS
TO
BIRTH 		NEOPLASM
DISEASESTAGE 		PATHOLOGY
T
STAGE 		PATHOLOGY
N
STAGE 		PATHOLOGY
M
STAGE 		RACE ETHNICITY
nMutated (%) nWild-Type logrank test Wilcoxon-test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test Fisher's exact test
CHD4 3 (2%) 127 9.29e-07
(0.000438) 		0.452
(1.00) 		0.289
(1.00) 		0.0709
(1.00) 		1
(1.00) 		0.00031
(0.0577) 		1
(1.00)
PIK3CD 3 (2%) 127 0.000367
(0.0577) 		0.471
(1.00) 		0.61
(1.00) 		0.368
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
KIT 25 (19%) 105 0.434
(1.00) 		0.107
(1.00) 		0.133
(1.00) 		0.603
(1.00) 		0.667
(1.00) 		1
(1.00) 		0.217
(1.00) 		0.687
(1.00)
KRAS 19 (15%) 111 0.388
(1.00) 		0.288
(1.00) 		0.588
(1.00) 		0.682
(1.00) 		1
(1.00) 		1
(1.00) 		0.781
(1.00) 		1
(1.00)
ANKLE1 11 (8%) 119 0.585
(1.00) 		0.688
(1.00) 		0.943
(1.00) 		0.444
(1.00) 		0.325
(1.00) 		1
(1.00) 		0.34
(1.00) 		1
(1.00)
FAM104B 6 (5%) 124 0.755
(1.00) 		0.665
(1.00) 		0.228
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.387
(1.00)
DDX11 6 (5%) 124 0.727
(1.00) 		0.0561
(1.00) 		0.25
(1.00) 		0.551
(1.00) 		1
(1.00) 		0.398
(1.00) 		1
(1.00)
NRAS 6 (5%) 124 0.755
(1.00) 		0.248
(1.00) 		0.34
(1.00) 		0.551
(1.00) 		1
(1.00) 		0.166
(1.00) 		1
(1.00)
PNPLA4 5 (4%) 125 0.711
(1.00) 		0.557
(1.00) 		0.296
(1.00) 		0.199
(1.00) 		1
(1.00) 		1
(1.00) 		0.323
(1.00)
SERINC2 3 (2%) 127 0.757
(1.00) 		0.744
(1.00) 		0.861
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
RBM10 4 (3%) 126 0.719
(1.00) 		0.919
(1.00) 		0.763
(1.00) 		0.708
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
DEK 5 (4%) 125 0.686
(1.00) 		0.505
(1.00) 		0.713
(1.00) 		0.722
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.387
(1.00)
ERC1 6 (5%) 124 0.711
(1.00) 		0.36
(1.00) 		0.327
(1.00) 		0.175
(1.00) 		0.515
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
HSF4 6 (5%) 124 0.678
(1.00) 		0.863
(1.00) 		0.4
(1.00) 		0.422
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
MUC6 13 (10%) 117 0.549
(1.00) 		0.689
(1.00) 		0.744
(1.00) 		0.479
(1.00) 		0.596
(1.00) 		1
(1.00) 		0.403
(1.00) 		1
(1.00)
FANK1 4 (3%) 126 0.777
(1.00) 		0.676
(1.00) 		0.226
(1.00) 		0.125
(1.00) 		1
(1.00) 		1
(1.00) 		0.323
(1.00)
MLLT3 3 (2%) 127 0.773
(1.00) 		0.0769
(1.00) 		0.403
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.252
(1.00)
RHPN2 6 (5%) 124 0.0506
(1.00) 		0.769
(1.00) 		0.349
(1.00) 		0.233
(1.00) 		1
(1.00) 		0.164
(1.00) 		1
(1.00) 		1
(1.00)
SP8 4 (3%) 126 0.777
(1.00) 		0.426
(1.00) 		0.414
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.323
(1.00)
KRTAP1-1 3 (2%) 127 0.827
(1.00) 		0.0304
(1.00) 		0.19
(1.00) 		1
(1.00) 		0.101
(1.00) 		1
(1.00)
ANKRD11 5 (4%) 125 0.686
(1.00) 		0.342
(1.00) 		0.812
(1.00) 		1
(1.00) 		1
(1.00) 		0.0524
(1.00) 		1
(1.00)
SPIN2A 3 (2%) 127 0.827
(1.00) 		0.16
(1.00) 		0.796
(1.00) 		0.623
(1.00) 		1
(1.00) 		1
(1.00) 		0.0219
(1.00)
ATXN3 3 (2%) 127 0.789
(1.00) 		0.816
(1.00) 		0.173
(1.00) 		1
(1.00) 		0.101
(1.00) 		1
(1.00) 		0.252
(1.00)
SSBP3 3 (2%) 127 0.789
(1.00) 		0.642
(1.00) 		0.547
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
KRTAP10-10 4 (3%) 126 0.747
(1.00) 		0.803
(1.00) 		0.953
(1.00) 		0.297
(1.00) 		1
(1.00) 		1
(1.00) 		0.323
(1.00)
BCL11B 5 (4%) 125 0.686
(1.00) 		0.0176
(1.00) 		0.515
(1.00) 		1
(1.00) 		1
(1.00) 		0.17
(1.00) 		1
(1.00)
FAM101B 4 (3%) 126 0.808
(1.00) 		0.691
(1.00) 		0.761
(1.00) 		0.708
(1.00) 		1
(1.00) 		0.032
(1.00) 		0.323
(1.00)
PSMD11 4 (3%) 126 0.827
(1.00) 		0.214
(1.00) 		0.831
(1.00) 		0.708
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
FAM8A1 3 (2%) 127 0.808
(1.00) 		0.846
(1.00) 		0.713
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
SPTAN1 3 (2%) 127 0.789
(1.00) 		0.1
(1.00) 		0.464
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.252
(1.00)
CRB2 6 (5%) 124 0.702
(1.00) 		0.351
(1.00) 		0.526
(1.00) 		0.551
(1.00) 		1
(1.00) 		1
(1.00) 		0.399
(1.00) 		1
(1.00)
OPLAH 4 (3%) 126 0.789
(1.00) 		0.808
(1.00) 		0.0475
(1.00) 		0.706
(1.00) 		0.133
(1.00) 		1
(1.00) 		1
(1.00)
GAS2L2 3 (2%) 127 0.789
(1.00) 		0.963
(1.00) 		0.403
(1.00) 		0.621
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
CDC27 6 (5%) 124 0.719
(1.00) 		0.773
(1.00) 		0.37
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.4
(1.00) 		1
(1.00)
MUC2 14 (11%) 116 0.533
(1.00) 		0.701
(1.00) 		0.191
(1.00) 		0.366
(1.00) 		1
(1.00) 		1
(1.00) 		0.681
(1.00) 		1
(1.00)
TPTE2 4 (3%) 126 0.795
(1.00) 		0.618
(1.00) 		0.42
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
NAT10 4 (3%) 126 0.777
(1.00) 		0.277
(1.00) 		0.886
(1.00) 		0.709
(1.00) 		1
(1.00) 		1
(1.00) 		0.323
(1.00)
INTS4 3 (2%) 127 0.789
(1.00) 		0.134
(1.00) 		0.641
(1.00) 		0.624
(1.00) 		1
(1.00) 		0.252
(1.00)
TTC38 4 (3%) 126 0.719
(1.00) 		0.544
(1.00) 		0.141
(1.00) 		0.195
(1.00) 		0.515
(1.00) 		0.133
(1.00) 		1
(1.00) 		1
(1.00)
RBM3 3 (2%) 127 0.789
(1.00) 		0.298
(1.00) 		0.0671
(1.00) 		0.624
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
TCHH 5 (4%) 125 0.686
(1.00) 		0.861
(1.00) 		0.0221
(1.00) 		0.724
(1.00) 		0.109
(1.00) 		1
(1.00) 		0.0507
(1.00) 		1
(1.00)
ZC3H11A 3 (2%) 127 0.757
(1.00) 		0.721
(1.00) 		0.0213
(1.00) 		1
(1.00) 		1
(1.00) 		0.223
(1.00) 		1
(1.00)
RAC1 4 (3%) 126 0.777
(1.00) 		0.28
(1.00) 		0.727
(1.00) 		0.0418
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
MTIF3 3 (2%) 127 0.773
(1.00) 		0.515
(1.00) 		1
(1.00) 		0.366
(1.00) 		1
(1.00) 		0.252
(1.00)
MFF 3 (2%) 127 0.757
(1.00) 		0.63
(1.00) 		0.37
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
PABPC3 3 (2%) 127 0.843
(1.00) 		0.238
(1.00) 		0.752
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
CUX1 5 (4%) 125 0.711
(1.00) 		0.153
(1.00) 		0.751
(1.00) 		0.138
(1.00) 		0.569
(1.00) 		1
(1.00) 		0.169
(1.00) 		1
(1.00)
PCMTD1 5 (4%) 125 0.711
(1.00) 		0.475
(1.00) 		0.245
(1.00) 		0.722
(1.00) 		1
(1.00) 		1
(1.00) 		0.343
(1.00) 		1
(1.00)
EZH2 4 (3%) 126 0.808
(1.00) 		0.362
(1.00) 		0.303
(1.00) 		0.128
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
HTT 3 (2%) 127 0.827
(1.00) 		0.244
(1.00) 		0.676
(1.00) 		0.191
(1.00) 		1
(1.00) 		1
(1.00) 		0.252
(1.00)
AHDC1 3 (2%) 127 0.757
(1.00) 		0.0937
(1.00) 		0.464
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
RFC3 3 (2%) 127 0.789
(1.00) 		0.203
(1.00) 		0.469
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.252
(1.00)
RUNX2 4 (3%) 126 0.777
(1.00) 		0.352
(1.00) 		0.652
(1.00) 		0.708
(1.00) 		1
(1.00) 		0.288
(1.00) 		1
(1.00)
SP4 3 (2%) 127 0.789
(1.00) 		0.438
(1.00) 		0.12
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
DIAPH1 3 (2%) 127 0.827
(1.00) 		0.0968
(1.00) 		0.0724
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
PLEC 6 (5%) 124 0.752
(1.00) 		0.125
(1.00) 		0.0522
(1.00) 		0.526
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
NHS 3 (2%) 127 0.757
(1.00) 		0.571
(1.00) 		0.329
(1.00) 		1
(1.00) 		0.515
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
EPAS1 4 (3%) 126 0.773
(1.00) 		0.122
(1.00) 		0.137
(1.00) 		0.368
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
DLC1 3 (2%) 127 0.843
(1.00) 		0.71
(1.00) 		0.362
(1.00) 		0.367
(1.00) 		1
(1.00) 		0.22
(1.00) 		1
(1.00)
'CHD4 MUTATION STATUS' versus 'Time to Death'

P value = 9.29e-07 (logrank test), Q value = 0.00044

Table S1.  Gene #51: 'CHD4 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 130 4 0.1 - 229.2 (38.0)
CHD4 MUTATED 3 1 0.4 - 41.7 (0.6)
CHD4 WILD-TYPE 127 3 0.1 - 229.2 (38.3)

Figure S1.  Get High-res Image Gene #51: 'CHD4 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'CHD4 MUTATION STATUS' versus 'RACE'

P value = 0.00031 (Fisher's exact test), Q value = 0.058

Table S2.  Gene #51: 'CHD4 MUTATION STATUS' versus Clinical Feature #7: 'RACE'

nPatients ASIAN BLACK OR AFRICAN AMERICAN WHITE
ALL 4 6 115
CHD4 MUTATED 1 2 0
CHD4 WILD-TYPE 3 4 115

Figure S2.  Get High-res Image Gene #51: 'CHD4 MUTATION STATUS' versus Clinical Feature #7: 'RACE'

'PIK3CD MUTATION STATUS' versus 'Time to Death'

P value = 0.000367 (logrank test), Q value = 0.058

Table S3.  Gene #57: 'PIK3CD MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 130 4 0.1 - 229.2 (38.0)
PIK3CD MUTATED 3 1 5.1 - 37.7 (20.3)
PIK3CD WILD-TYPE 127 3 0.1 - 229.2 (39.4)

Figure S3.  Get High-res Image Gene #57: 'PIK3CD MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

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/TGCT-TP/15890413/transformed.cor.cli.txt

  • Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/TGCT-TP/15092576/TGCT-TP.merged_data.txt

  • Number of patients = 130

  • Number of significantly mutated genes = 59

  • 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.

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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