Skin Cutaneous Melanoma: Correlation between gene mutation status and selected clinical features
(metastatic tumor cohort)
Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)
Overview
Introduction

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

Summary

Testing the association between mutation status of 149 genes and 3 clinical features across 139 patients, 2 significant findings detected with Q value < 0.25.

  • MUC7 mutation correlated to 'AGE'.

  • KRT26 mutation correlated to 'Time to Death'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 149 genes and 3 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 2 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE GENDER
nMutated (%) nWild-Type logrank test t-test Fisher's exact test
MUC7 11 (8%) 128 0.495
(1.00) 		0.000211
(0.0941) 		0.746
(1.00)
KRT26 7 (5%) 132 6.86e-06
(0.00307) 		0.741
(1.00) 		1
(1.00)
BRAF 69 (50%) 70 0.123
(1.00) 		0.0503
(1.00) 		1
(1.00)
NRAS 43 (31%) 96 0.8
(1.00) 		0.164
(1.00) 		0.85
(1.00)
CDKN2A 21 (15%) 118 0.638
(1.00) 		0.532
(1.00) 		1
(1.00)
TP53 25 (18%) 114 0.464
(1.00) 		0.0985
(1.00) 		0.819
(1.00)
PTEN 9 (6%) 130 0.857
(1.00) 		0.798
(1.00) 		0.725
(1.00)
ACSM2B 28 (20%) 111 0.146
(1.00) 		0.952
(1.00) 		0.00764
(1.00)
LCE1B 9 (6%) 130 0.586
(1.00) 		0.671
(1.00) 		0.725
(1.00)
CADM2 15 (11%) 124 0.792
(1.00) 		0.888
(1.00) 		1
(1.00)
NAP1L2 12 (9%) 127 0.689
(1.00) 		0.0733
(1.00) 		0.759
(1.00)
RAC1 11 (8%) 128 0.0429
(1.00) 		0.537
(1.00) 		1
(1.00)
OR51S1 16 (12%) 123 0.415
(1.00) 		0.54
(1.00) 		1
(1.00)
FUT9 16 (12%) 123 0.954
(1.00) 		0.0278
(1.00) 		1
(1.00)
PPP6C 13 (9%) 126 0.0385
(1.00) 		0.767
(1.00) 		0.768
(1.00)
USP29 25 (18%) 114 0.0456
(1.00) 		0.092
(1.00) 		0.367
(1.00)
RPTN 22 (16%) 117 0.545
(1.00) 		0.373
(1.00) 		0.81
(1.00)
TAF1A 8 (6%) 131 0.275
(1.00) 		0.577
(1.00) 		0.465
(1.00)
CDH9 25 (18%) 114 0.333
(1.00) 		0.469
(1.00) 		1
(1.00)
GRXCR1 14 (10%) 125 0.405
(1.00) 		0.0188
(1.00) 		0.573
(1.00)
HIST1H2AA 7 (5%) 132 0.901
(1.00) 		0.99
(1.00) 		0.707
(1.00)
ZNF679 14 (10%) 125 0.952
(1.00) 		0.434
(1.00) 		0.573
(1.00)
C8A 17 (12%) 122 0.00454
(1.00) 		0.00429
(1.00) 		0.0299
(1.00)
RBM11 10 (7%) 129 0.69
(1.00) 		0.288
(1.00) 		0.746
(1.00)
ZNF479 12 (9%) 127 0.36
(1.00) 		0.0896
(1.00) 		0.759
(1.00)
GFRAL 20 (14%) 119 0.473
(1.00) 		0.643
(1.00) 		1
(1.00)
DDX3X 15 (11%) 124 0.613
(1.00) 		0.467
(1.00) 		0.256
(1.00)
OR4M2 16 (12%) 123 0.65
(1.00) 		0.0859
(1.00) 		1
(1.00)
FRG2B 10 (7%) 129 0.503
(1.00) 		0.0228
(1.00) 		0.498
(1.00)
PDE1A 23 (17%) 116 0.309
(1.00) 		0.162
(1.00) 		1
(1.00)
PRB2 21 (15%) 118 0.548
(1.00) 		0.0129
(1.00) 		0.0867
(1.00)
LUZP2 12 (9%) 127 0.651
(1.00) 		0.908
(1.00) 		0.759
(1.00)
NRK 18 (13%) 121 0.34
(1.00) 		0.821
(1.00) 		0.8
(1.00)
PARM1 11 (8%) 128 0.00851
(1.00) 		0.214
(1.00) 		1
(1.00)
SLC38A4 16 (12%) 123 0.786
(1.00) 		0.352
(1.00) 		0.168
(1.00)
PRAMEF11 12 (9%) 127 0.187
(1.00) 		0.151
(1.00) 		0.759
(1.00)
USP17L2 13 (9%) 126 0.64
(1.00) 		0.928
(1.00) 		0.373
(1.00)
PRB1 12 (9%) 127 0.33
(1.00) 		0.554
(1.00) 		0.21
(1.00)
CYLC2 16 (12%) 123 0.616
(1.00) 		0.104
(1.00) 		0.785
(1.00)
DSG3 33 (24%) 106 0.649
(1.00) 		0.134
(1.00) 		0.416
(1.00)
VEGFC 11 (8%) 128 0.943
(1.00) 		0.414
(1.00) 		1
(1.00)
IL32 5 (4%) 134 0.0263
(1.00) 		0.484
(1.00) 		1
(1.00)
LILRB4 21 (15%) 118 0.24
(1.00) 		0.385
(1.00) 		0.81
(1.00)
GLRB 15 (11%) 124 0.478
(1.00) 		0.114
(1.00) 		1
(1.00)
STXBP5L 29 (21%) 110 0.12
(1.00) 		0.538
(1.00) 		0.523
(1.00)
GML 8 (6%) 131 0.932
(1.00) 		0.117
(1.00) 		0.258
(1.00)
TLL1 30 (22%) 109 0.373
(1.00) 		0.235
(1.00) 		0.522
(1.00)
DEFB118 6 (4%) 133 0.141
(1.00) 		0.435
(1.00) 		1
(1.00)
GK2 17 (12%) 122 0.199
(1.00) 		0.968
(1.00) 		1
(1.00)
OR5J2 10 (7%) 129 0.824
(1.00) 		0.942
(1.00) 		0.171
(1.00)
LIN7A 8 (6%) 131 0.412
(1.00) 		0.736
(1.00) 		0.71
(1.00)
MUM1L1 13 (9%) 126 0.357
(1.00) 		0.55
(1.00) 		0.768
(1.00)
MARCH11 7 (5%) 132 0.336
(1.00) 		0.954
(1.00) 		1
(1.00)
PSG4 15 (11%) 124 0.969
(1.00) 		0.462
(1.00) 		0.783
(1.00)
ZIM3 12 (9%) 127 0.0468
(1.00) 		0.968
(1.00) 		0.535
(1.00)
CLEC14A 14 (10%) 125 0.262
(1.00) 		0.905
(1.00) 		0.255
(1.00)
OR5H2 11 (8%) 128 0.421
(1.00) 		0.032
(1.00) 		0.532
(1.00)
TCEB3C 20 (14%) 119 0.508
(1.00) 		0.148
(1.00) 		0.0429
(1.00)
PRB4 16 (12%) 123 0.137
(1.00) 		0.263
(1.00) 		0.412
(1.00)
KLHL4 14 (10%) 125 0.147
(1.00) 		0.666
(1.00) 		0.381
(1.00)
OR52J3 8 (6%) 131 0.149
(1.00) 		0.425
(1.00) 		1
(1.00)
HBD 8 (6%) 131 0.0833
(1.00) 		0.632
(1.00) 		0.465
(1.00)
FAM19A1 7 (5%) 132 0.338
(1.00) 		0.978
(1.00) 		0.707
(1.00)
LRRIQ4 14 (10%) 125 0.449
(1.00) 		0.152
(1.00) 		0.381
(1.00)
SPINK13 4 (3%) 135 0.182
(1.00) 		0.341
(1.00) 		1
(1.00)
SNAP91 17 (12%) 122 0.913
(1.00) 		0.0687
(1.00) 		0.289
(1.00)
LONRF2 10 (7%) 129 0.0751
(1.00) 		0.888
(1.00) 		0.746
(1.00)
CLCC1 7 (5%) 132 0.127
(1.00) 		0.54
(1.00) 		1
(1.00)
KIAA1257 7 (5%) 132 0.0824
(1.00) 		0.0293
(1.00) 		0.423
(1.00)
SIGLEC14 6 (4%) 133 0.872
(1.00) 		0.165
(1.00) 		0.0854
(1.00)
SPANXN2 12 (9%) 127 0.0283
(1.00) 		0.776
(1.00) 		0.535
(1.00)
DEFB112 5 (4%) 134 0.307
(1.00) 		0.282
(1.00) 		1
(1.00)
CD2 14 (10%) 125 0.592
(1.00) 		0.357
(1.00) 		0.771
(1.00)
HTR3B 9 (6%) 130 0.0558
(1.00) 		0.889
(1.00) 		0.154
(1.00)
KIR2DL1 9 (6%) 130 0.412
(1.00) 		0.354
(1.00) 		0.725
(1.00)
OR4N2 17 (12%) 122 0.832
(1.00) 		0.373
(1.00) 		0.0299
(1.00)
ST18 27 (19%) 112 0.791
(1.00) 		0.387
(1.00) 		0.825
(1.00)
TUBB8 7 (5%) 132 0.898
(1.00) 		0.202
(1.00) 		1
(1.00)
C2ORF40 4 (3%) 135 0.732
(1.00) 		0.414
(1.00) 		0.624
(1.00)
PRR23B 9 (6%) 130 0.374
(1.00) 		0.421
(1.00) 		0.725
(1.00)
TFEC 12 (9%) 127 0.199
(1.00) 		0.0329
(1.00) 		0.759
(1.00)
SGCZ 15 (11%) 124 0.0793
(1.00) 		0.868
(1.00) 		1
(1.00)
TRAT1 9 (6%) 130 0.04
(1.00) 		0.681
(1.00) 		0.725
(1.00)
TRIM58 12 (9%) 127 0.415
(1.00) 		0.00268
(1.00) 		1
(1.00)
ANXA10 9 (6%) 130 0.346
(1.00) 		0.248
(1.00) 		0.486
(1.00)
ZNF844 4 (3%) 135 0.426
(1.00) 		0.0198
(1.00) 		0.624
(1.00)
SLC14A1 10 (7%) 129 0.693
(1.00) 		0.129
(1.00) 		0.0136
(1.00)
C9 11 (8%) 128 0.462
(1.00) 		0.897
(1.00) 		0.532
(1.00)
DSG1 21 (15%) 118 0.105
(1.00) 		0.397
(1.00) 		1
(1.00)
CCDC11 13 (9%) 126 0.783
(1.00) 		0.962
(1.00) 		1
(1.00)
MKX 10 (7%) 129 0.476
(1.00) 		0.837
(1.00) 		0.746
(1.00)
OR7D2 13 (9%) 126 0.925
(1.00) 		0.522
(1.00) 		0.373
(1.00)
STARD6 5 (4%) 134 0.848
(1.00) 		0.0446
(1.00) 		1
(1.00)
SPATA8 5 (4%) 134 0.576
(1.00) 		0.0871
(1.00) 		0.356
(1.00)
GRXCR2 11 (8%) 128 0.38
(1.00) 		0.756
(1.00) 		1
(1.00)
OR4A15 14 (10%) 125 0.983
(1.00) 		0.0485
(1.00) 		0.0827
(1.00)
C4ORF22 8 (6%) 131 0.281
(1.00) 		0.614
(1.00) 		0.71
(1.00)
CCDC54 10 (7%) 129 0.468
(1.00) 		0.699
(1.00) 		0.325
(1.00)
CRISP2 8 (6%) 131 0.955
(1.00) 		0.0943
(1.00) 		0.465
(1.00)
MOG 6 (4%) 133 0.866
(1.00) 		0.0659
(1.00) 		0.414
(1.00)
NMS 7 (5%) 132 0.948
(1.00) 		0.169
(1.00) 		0.707
(1.00)
DEFB115 5 (4%) 134 0.935
(1.00) 		0.515
(1.00) 		0.158
(1.00)
UGT2A3 12 (9%) 127 0.999
(1.00) 		0.476
(1.00) 		0.535
(1.00)
ZNF98 12 (9%) 127 0.16
(1.00) 		0.826
(1.00) 		0.759
(1.00)
ADH1C 22 (16%) 117 0.628
(1.00) 		0.242
(1.00) 		0.81
(1.00)
HBG2 6 (4%) 133 0.626
(1.00) 		0.254
(1.00) 		1
(1.00)
HHLA2 9 (6%) 130 0.649
(1.00) 		0.333
(1.00) 		1
(1.00)
IDH1 7 (5%) 132 0.802
(1.00) 		0.0116
(1.00) 		0.261
(1.00)
OR2L3 10 (7%) 129 0.477
(1.00) 		0.703
(1.00) 		0.746
(1.00)
OR4F6 10 (7%) 129 0.166
(1.00) 		0.314
(1.00) 		0.325
(1.00)
B2M 4 (3%) 135 0.685
(1.00) 		0.388
(1.00) 		0.296
(1.00)
ARID2 20 (14%) 119 0.22
(1.00) 		0.151
(1.00) 		0.319
(1.00)
LOC649330 16 (12%) 123 0.288
(1.00) 		0.0226
(1.00) 		0.785
(1.00)
OR5AC2 14 (10%) 125 0.916
(1.00) 		0.764
(1.00) 		0.573
(1.00)
OR5H14 7 (5%) 132 0.357
(1.00) 		0.83
(1.00) 		0.0472
(1.00)
SPAG16 12 (9%) 127 0.251
(1.00) 		0.511
(1.00) 		0.21
(1.00)
SPRY3 8 (6%) 131 0.273
(1.00) 		0.289
(1.00) 		1
(1.00)
STK31 22 (16%) 117 0.825
(1.00) 		0.711
(1.00) 		1
(1.00)
TACR3 13 (9%) 126 0.178
(1.00) 		0.951
(1.00) 		0.768
(1.00)
SERPINB4 18 (13%) 121 0.969
(1.00) 		0.153
(1.00) 		0.0695
(1.00)
TSGA13 6 (4%) 133 0.307
(1.00) 		0.908
(1.00) 		0.414
(1.00)
GIMAP7 11 (8%) 128 0.816
(1.00) 		0.0828
(1.00) 		0.328
(1.00)
SDR16C5 18 (13%) 121 0.603
(1.00) 		0.121
(1.00) 		0.446
(1.00)
SPOCK3 16 (12%) 123 0.739
(1.00) 		0.565
(1.00) 		0.0507
(1.00)
TRHR 15 (11%) 124 0.154
(1.00) 		0.377
(1.00) 		1
(1.00)
CD96 10 (7%) 129 0.92
(1.00) 		0.451
(1.00) 		1
(1.00)
CLEC4E 10 (7%) 129 0.447
(1.00) 		0.245
(1.00) 		0.498
(1.00)
TPTE 36 (26%) 103 0.702
(1.00) 		0.199
(1.00) 		0.691
(1.00)
MCART6 7 (5%) 132 0.763
(1.00) 		0.077
(1.00) 		1
(1.00)
OR2W1 12 (9%) 127 0.726
(1.00) 		0.0799
(1.00) 		0.357
(1.00)
MORF4 10 (7%) 129 0.527
(1.00) 		0.829
(1.00) 		0.746
(1.00)
RGS18 7 (5%) 132 0.981
(1.00) 		0.35
(1.00) 		0.0472
(1.00)
BAGE2 9 (6%) 130 0.806
(1.00) 		0.916
(1.00) 		0.725
(1.00)
KIAA1644 4 (3%) 135 0.388
(1.00) 		0.24
(1.00) 		1
(1.00)
AGXT2 14 (10%) 125 0.205
(1.00) 		0.452
(1.00) 		1
(1.00)
CLDN4 7 (5%) 132 0.914
(1.00) 		0.0532
(1.00) 		0.707
(1.00)
CDH10 21 (15%) 118 0.0274
(1.00) 		0.99
(1.00) 		0.81
(1.00)
VWC2L 11 (8%) 128 0.777
(1.00) 		0.884
(1.00) 		1
(1.00)
ABRA 10 (7%) 129 0.0738
(1.00) 		0.062
(1.00) 		0.325
(1.00)
ARPP21 23 (17%) 116 0.126
(1.00) 		0.0809
(1.00) 		0.154
(1.00)
NR1H4 8 (6%) 131 0.37
(1.00) 		0.287
(1.00) 		0.71
(1.00)
GZMA 8 (6%) 131 0.964
(1.00) 		0.376
(1.00) 		0.71
(1.00)
DGAT2L6 8 (6%) 131 0.504
(1.00) 		0.459
(1.00) 		1
(1.00)
TMCO5A 6 (4%) 133 0.392
(1.00) 		0.275
(1.00) 		0.414
(1.00)
CCNE2 7 (5%) 132 0.136
(1.00) 		0.73
(1.00) 		0.707
(1.00)
CCK 5 (4%) 134 0.128
(1.00) 		0.744
(1.00) 		0.652
(1.00)
ADAMTS20 35 (25%) 104 0.391
(1.00) 		0.13
(1.00) 		0.312
(1.00)
MPP7 17 (12%) 122 0.86
(1.00) 		0.0249
(1.00) 		0.599
(1.00)
FAM155A 9 (6%) 130 0.193
(1.00) 		0.595
(1.00) 		0.288
(1.00)
'MUC7 MUTATION STATUS' versus 'AGE'

P value = 0.000211 (t-test), Q value = 0.094

Table S1.  Gene #11: 'MUC7 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 137 56.5 (16.2)
MUC7 MUTATED 11 72.7 (10.9)
MUC7 WILD-TYPE 126 55.0 (15.8)

Figure S1.  Get High-res Image Gene #11: 'MUC7 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'KRT26 MUTATION STATUS' versus 'Time to Death'

P value = 6.86e-06 (logrank test), Q value = 0.0031

Table S2.  Gene #144: 'KRT26 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 136 67 0.2 - 346.0 (47.5)
KRT26 MUTATED 7 6 2.6 - 44.4 (18.6)
KRT26 WILD-TYPE 129 61 0.2 - 346.0 (48.9)

Figure S2.  Get High-res Image Gene #144: 'KRT26 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

Methods & Data
Input

  • Mutation data file = SKCM-TM.mutsig.cluster.txt

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

  • Number of patients = 139

  • Number of significantly mutated genes = 149

  • Number of selected clinical features = 3

  • 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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