Skin Cutaneous Melanoma: Correlation between gene mutation status and selected clinical features
(NRAS_Hotspot_Mutants 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 99 genes and 7 clinical features across 45 patients, 3 significant findings detected with Q value < 0.25.

  • TP53 mutation correlated to 'AGE'.

  • CLEC17A mutation correlated to 'AGE'.

  • OR4M2 mutation correlated to 'AGE'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 99 genes and 7 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 PRIMARY
SITE
OF
DISEASE 		GENDER LYMPH
NODE
METASTASIS 		TUMOR
STAGECODE 		NEOPLASM
DISEASESTAGE
nMutated (%) nWild-Type logrank test t-test Fisher's exact test Fisher's exact test Chi-square test t-test Chi-square test
TP53 9 (20%) 36 0.784
(1.00) 		0.000119
(0.0651) 		0.659
(1.00) 		1
(1.00) 		0.129
(1.00) 		0.384
(1.00)
CLEC17A 3 (7%) 42 4.55e-07
(0.00025) 		1
(1.00) 		1
(1.00) 		0.0784
(1.00) 		0.458
(1.00)
OR4M2 6 (13%) 39 0.554
(1.00) 		0.000255
(0.14) 		0.397
(1.00) 		1
(1.00) 		0.526
(1.00) 		0.339
(1.00)
CDKN2A 11 (24%) 34 0.341
(1.00) 		0.782
(1.00) 		0.286
(1.00) 		0.483
(1.00) 		0.23
(1.00) 		0.25
(1.00)
MUM1L1 7 (16%) 38 0.553
(1.00) 		0.754
(1.00) 		0.162
(1.00) 		0.686
(1.00) 		0.0038
(1.00) 		0.314
(1.00)
CD163L1 13 (29%) 32 0.604
(1.00) 		0.00256
(1.00) 		0.9
(1.00) 		0.743
(1.00) 		0.582
(1.00) 		0.709
(1.00)
PSG4 8 (18%) 37 0.521
(1.00) 		0.259
(1.00) 		0.427
(1.00) 		0.822
(1.00) 		0.971
(1.00)
PPP6C 9 (20%) 36 0.659
(1.00) 		0.414
(1.00) 		0.0712
(1.00) 		0.7
(1.00) 		0.0595
(1.00) 		0.348
(1.00)
ZNF99 13 (29%) 32 0.14
(1.00) 		0.135
(1.00) 		0.47
(1.00) 		0.494
(1.00) 		0.678
(1.00) 		0.532
(1.00)
KHDRBS2 8 (18%) 37 0.249
(1.00) 		0.0923
(1.00) 		0.259
(1.00) 		0.691
(1.00) 		0.745
(1.00) 		0.651
(1.00)
POTEG 8 (18%) 37 0.258
(1.00) 		0.257
(1.00) 		0.628
(1.00) 		0.691
(1.00) 		0.418
(1.00) 		0.606
(1.00)
MARCO 9 (20%) 36 0.275
(1.00) 		0.936
(1.00) 		0.21
(1.00) 		0.127
(1.00) 		0.285
(1.00) 		0.348
(1.00)
SGCZ 8 (18%) 37 0.148
(1.00) 		0.829
(1.00) 		0.628
(1.00) 		1
(1.00) 		0.278
(1.00) 		0.546
(1.00)
GLRB 9 (20%) 36 0.000817
(0.447) 		0.434
(1.00) 		0.432
(1.00) 		0.456
(1.00) 		0.778
(1.00) 		0.502
(1.00)
OR2W1 6 (13%) 39 0.0388
(1.00) 		0.473
(1.00) 		0.703
(1.00) 		1
(1.00) 		0.471
(1.00) 		0.555
(1.00)
C4ORF22 5 (11%) 40 0.728
(1.00) 		0.826
(1.00) 		0.656
(1.00) 		1
(1.00) 		0.773
(1.00) 		0.773
(1.00)
UGT2B28 8 (18%) 37 0.515
(1.00) 		0.164
(1.00) 		0.869
(1.00) 		1
(1.00) 		0.653
(1.00) 		0.883
(1.00)
ZNF676 10 (22%) 35 0.779
(1.00) 		0.687
(1.00) 		0.459
(1.00) 		0.726
(1.00) 		0.604
(1.00) 		0.606
(1.00)
LIPI 7 (16%) 38 0.355
(1.00) 		0.721
(1.00) 		1
(1.00) 		0.393
(1.00) 		0.471
(1.00) 		0.92
(1.00)
CADM2 5 (11%) 40 0.504
(1.00) 		0.764
(1.00) 		0.426
(1.00) 		0.33
(1.00) 		0.0934
(1.00) 		0.036
(1.00)
CDH9 9 (20%) 36 0.723
(1.00) 		0.728
(1.00) 		0.283
(1.00) 		0.7
(1.00) 		0.672
(1.00) 		0.344
(1.00)
OR52E2 6 (13%) 39 0.991
(1.00) 		0.493
(1.00) 		1
(1.00) 		0.865
(1.00) 		0.528
(1.00)
CLEC5A 4 (9%) 41 0.471
(1.00) 		0.215
(1.00) 		0.281
(1.00) 		0.799
(1.00) 		0.155
(1.00)
HIST1H2AA 3 (7%) 42 0.438
(1.00) 		0.76
(1.00) 		1
(1.00) 		0.877
(1.00) 		0.779
(1.00)
KIAA1257 4 (9%) 41 0.531
(1.00) 		0.0896
(1.00) 		1
(1.00) 		0.373
(1.00) 		0.154
(1.00)
PCDH18 9 (20%) 36 0.756
(1.00) 		0.865
(1.00) 		0.659
(1.00) 		1
(1.00) 		0.817
(1.00) 		0.989
(1.00)
SPOCK3 6 (13%) 39 0.63
(1.00) 		0.189
(1.00) 		0.0749
(1.00) 		0.566
(1.00) 		0.0919
(1.00)
OR2G6 8 (18%) 37 0.359
(1.00) 		0.00686
(1.00) 		0.215
(1.00) 		1
(1.00) 		0.809
(1.00) 		0.949
(1.00)
STXBP5L 10 (22%) 35 0.313
(1.00) 		0.726
(1.00) 		0.601
(1.00) 		0.131
(1.00) 		0.268
(1.00) 		0.897
(1.00)
CNGB3 9 (20%) 36 0.0345
(1.00) 		0.335
(1.00) 		1
(1.00) 		0.017
(1.00) 		0.778
(1.00) 		0.717
(1.00)
HHIPL2 3 (7%) 42 0.696
(1.00) 		1
(1.00) 		0.285
(1.00) 		0.847
(1.00) 		0.936
(1.00)
OR10G8 4 (9%) 41 0.224
(1.00) 		0.802
(1.00) 		0.121
(1.00) 		0.257
(1.00) 		0.458
(1.00)
UGT2B4 8 (18%) 37 0.684
(1.00) 		0.375
(1.00) 		0.869
(1.00) 		0.427
(1.00) 		0.512
(1.00) 		0.071
(1.00)
ZBBX 9 (20%) 36 0.118
(1.00) 		0.583
(1.00) 		0.659
(1.00) 		0.127
(1.00) 		0.357
(1.00) 		0.441
(1.00)
C1QTNF9 3 (7%) 42 0.824
(1.00) 		1
(1.00) 		1
(1.00) 		0.877
(1.00) 		0.564
(1.00)
HCRTR2 7 (16%) 38 0.213
(1.00) 		0.123
(1.00) 		0.522
(1.00) 		1
(1.00) 		0.598
(1.00) 		0.355
(1.00)
KRT78 5 (11%) 40 0.236
(1.00) 		0.276
(1.00) 		0.807
(1.00) 		1
(1.00) 		0.448
(1.00) 		0.461
(1.00)
BCLAF1 9 (20%) 36 0.118
(1.00) 		0.0172
(1.00) 		0.378
(1.00) 		0.456
(1.00) 		0.809
(1.00) 		0.789
(1.00)
LPAR1 3 (7%) 42 0.269
(1.00) 		0.529
(1.00) 		0.542
(1.00) 		0.735
(1.00) 		0.779
(1.00)
STK31 6 (13%) 39 0.0311
(1.00) 		0.935
(1.00) 		0.189
(1.00) 		1
(1.00) 		0.46
(1.00) 		0.667
(1.00)
HBG2 4 (9%) 41 0.123
(1.00) 		0.802
(1.00) 		1
(1.00) 		0.799
(1.00) 		0.608
(1.00)
BAGE2 3 (7%) 42 0.29
(1.00) 		0.103
(1.00) 		1
(1.00) 		0.847
(1.00) 		0.564
(1.00)
ADH1B 6 (13%) 39 0.605
(1.00) 		0.595
(1.00) 		0.65
(1.00) 		0.877
(1.00) 		0.461
(1.00)
CNTN4 10 (22%) 35 0.833
(1.00) 		0.681
(1.00) 		0.139
(1.00) 		1
(1.00) 		0.355
(1.00) 		0.7
(1.00)
DEFA4 4 (9%) 41 0.979
(1.00) 		0.802
(1.00) 		0.608
(1.00) 		0.88
(1.00) 		0.196
(1.00)
GFRAL 8 (18%) 37 0.579
(1.00) 		0.78
(1.00) 		0.141
(1.00) 		0.427
(1.00) 		0.546
(1.00) 		0.00422
(1.00)
ST8SIA3 6 (13%) 39 0.416
(1.00) 		0.768
(1.00) 		0.595
(1.00) 		0.166
(1.00) 		0.0355
(1.00) 		0.597
(1.00)
DSPP 5 (11%) 40 0.7
(1.00) 		0.336
(1.00) 		1
(1.00) 		0.448
(1.00) 		0.461
(1.00)
OR10K2 7 (16%) 38 0.0489
(1.00) 		0.0419
(1.00) 		1
(1.00) 		1
(1.00) 		0.364
(1.00) 		0.734
(1.00)
POU6F2 8 (18%) 37 0.645
(1.00) 		0.0106
(1.00) 		0.869
(1.00) 		1
(1.00) 		0.0796
(1.00) 		0.467
(1.00)
LRRIQ3 7 (16%) 38 0.349
(1.00) 		0.341
(1.00) 		1
(1.00) 		1
(1.00) 		0.231
(1.00) 		0.497
(1.00)
ARID2 9 (20%) 36 0.0875
(1.00) 		0.659
(1.00) 		0.456
(1.00) 		0.7
(1.00) 		0.753
(1.00)
GAS2 5 (11%) 40 0.973
(1.00) 		0.256
(1.00) 		0.641
(1.00) 		0.676
(1.00) 		0.242
(1.00)
SIRPB1 6 (13%) 39 0.97
(1.00) 		0.669
(1.00) 		0.703
(1.00) 		0.399
(1.00) 		0.763
(1.00) 		0.986
(1.00)
ACTC1 4 (9%) 41 0.709
(1.00) 		0.619
(1.00) 		0.281
(1.00) 		0.773
(1.00) 		0.196
(1.00)
PRB2 5 (11%) 40 0.167
(1.00) 		0.193
(1.00) 		0.656
(1.00) 		0.144
(1.00) 		0.306
(1.00) 		0.905
(1.00)
C15ORF23 3 (7%) 42 0.533
(1.00) 		0.316
(1.00) 		1
(1.00) 		0.0296
(1.00) 		0.112
(1.00)
FASLG 3 (7%) 42 0.569
(1.00) 		0.76
(1.00) 		1
(1.00)
PAK7 9 (20%) 36 0.693
(1.00) 		0.288
(1.00) 		0.659
(1.00) 		1
(1.00) 		0.21
(1.00) 		0.512
(1.00)
SIGLEC14 3 (7%) 42 0.256
(1.00) 		0.0276
(1.00) 		0.542
(1.00) 		0.533
(1.00) 		0.564
(1.00)
TPTE2 6 (13%) 39 0.915
(1.00) 		0.599
(1.00) 		0.595
(1.00) 		0.399
(1.00) 		0.773
(1.00) 		0.693
(1.00)
APBB1IP 5 (11%) 40 0.189
(1.00) 		0.746
(1.00) 		0.522
(1.00) 		1
(1.00) 		0.448
(1.00) 		0.667
(1.00)
ANGPT1 6 (13%) 39 0.208
(1.00) 		0.509
(1.00) 		0.703
(1.00) 		0.0749
(1.00) 		0.761
(1.00) 		0.882
(1.00)
ARMC4 11 (24%) 34 0.268
(1.00) 		0.11
(1.00) 		0.477
(1.00) 		1
(1.00) 		0.143
(1.00) 		0.748
(1.00)
CYP4X1 4 (9%) 41 0.055
(1.00) 		0.306
(1.00) 		0.121
(1.00) 		0.0503
(1.00) 		0.905
(1.00)
DSG1 6 (13%) 39 0.961
(1.00) 		0.58
(1.00) 		0.397
(1.00) 		0.65
(1.00) 		0.0552
(1.00) 		0.615
(1.00)
ADAM7 10 (22%) 35 0.184
(1.00) 		0.809
(1.00) 		0.337
(1.00) 		0.0714
(1.00) 		0.68
(1.00) 		0.67
(1.00)
KCNQ5 8 (18%) 37 0.068
(1.00) 		0.421
(1.00) 		0.468
(1.00) 		1
(1.00) 		0.945
(1.00) 		0.967
(1.00)
POF1B 8 (18%) 37 0.823
(1.00) 		0.652
(1.00) 		0.215
(1.00) 		0.427
(1.00) 		0.164
(1.00) 		0.703
(1.00)
TCEB3C 6 (13%) 39 0.578
(1.00) 		0.91
(1.00) 		1
(1.00) 		0.399
(1.00) 		0.182
(1.00) 		0.732
(1.00)
F2RL1 5 (11%) 40 0.221
(1.00) 		0.522
(1.00) 		0.33
(1.00) 		0.88
(1.00) 		0.608
(1.00)
SNCAIP 9 (20%) 36 0.307
(1.00) 		0.9
(1.00) 		1
(1.00) 		0.127
(1.00) 		0.473
(1.00) 		0.746
(1.00)
LOC649330 7 (16%) 38 0.84
(1.00) 		0.207
(1.00) 		1
(1.00) 		1
(1.00) 		0.471
(1.00) 		0.838
(1.00)
UGT2A3 6 (13%) 39 0.211
(1.00) 		0.493
(1.00) 		0.399
(1.00) 		0.761
(1.00) 		0.217
(1.00)
NDUFA13 4 (9%) 41 0.478
(1.00) 		0.118
(1.00) 		0.444
(1.00) 		0.281
(1.00) 		0.218
(1.00) 		0.773
(1.00)
ZIM3 4 (9%) 41 0.884
(1.00) 		1
(1.00) 		1
(1.00) 		0.877
(1.00) 		0.869
(1.00)
DDX3X 6 (13%) 39 0.971
(1.00) 		0.819
(1.00) 		0.399
(1.00) 		0.676
(1.00) 		0.798
(1.00)
LILRB4 6 (13%) 39 0.579
(1.00) 		0.0544
(1.00) 		0.65
(1.00) 		0.911
(1.00) 		0.157
(1.00)
TLR4 9 (20%) 36 0.857
(1.00) 		0.854
(1.00) 		0.378
(1.00) 		0.127
(1.00) 		0.608
(1.00) 		0.546
(1.00)
ZNF479 3 (7%) 42 0.0535
(1.00) 		1
(1.00) 		1
(1.00) 		0.0151
(1.00) 		0.936
(1.00)
GABRG1 3 (7%) 42 0.297
(1.00) 		0.76
(1.00) 		1
(1.00) 		0.257
(1.00) 		0.779
(1.00)
OR1N2 6 (13%) 39 0.827
(1.00) 		0.493
(1.00) 		0.399
(1.00) 		0.761
(1.00) 		0.441
(1.00)
HHLA2 4 (9%) 41 0.726
(1.00) 		0.215
(1.00) 		0.281
(1.00) 		0.799
(1.00) 		0.693
(1.00)
SYCE1 4 (9%) 41 0.0737
(1.00) 		0.215
(1.00) 		1
(1.00) 		0.0296
(1.00) 		0.0797
(1.00)
RGPD3 9 (20%) 36 0.816
(1.00) 		0.543
(1.00) 		0.766
(1.00) 		0.456
(1.00) 		0.628
(1.00) 		0.424
(1.00)
CDH10 10 (22%) 35 0.241
(1.00) 		0.454
(1.00) 		0.774
(1.00) 		0.726
(1.00) 		0.0475
(1.00) 		0.422
(1.00)
C6ORF105 4 (9%) 41 0.00357
(1.00) 		1
(1.00) 		1
(1.00) 		0.00399
(1.00) 		0.155
(1.00)
FPR2 4 (9%) 41 0.834
(1.00) 		0.619
(1.00) 		1
(1.00) 		0.783
(1.00) 		0.693
(1.00)
UGT1A7 3 (7%) 42 0.389
(1.00) 		1
(1.00) 		1
(1.00) 		0.257
(1.00) 		0.779
(1.00)
JAKMIP1 5 (11%) 40 0.00949
(1.00) 		1
(1.00) 		0.641
(1.00) 		0.865
(1.00) 		0.0719
(1.00)
CYLC2 5 (11%) 40 0.256
(1.00) 		1
(1.00) 		0.641
(1.00) 		0.404
(1.00) 		0.773
(1.00)
DRGX 6 (13%) 39 0.368
(1.00) 		0.595
(1.00) 		1
(1.00) 		0.761
(1.00) 		0.615
(1.00)
IDH1 3 (7%) 42 0.401
(1.00) 		0.76
(1.00) 		0.285
(1.00) 		0.877
(1.00) 		0.779
(1.00)
ASB5 3 (7%) 42 0.37
(1.00) 		1
(1.00) 		1
(1.00) 		0.877
(1.00) 		0.674
(1.00)
COL21A1 9 (20%) 36 0.289
(1.00) 		0.684
(1.00) 		0.766
(1.00) 		0.456
(1.00) 		0.496
(1.00) 		0.0164
(1.00)
ANKRD45 7 (16%) 38 0.791
(1.00) 		0.114
(1.00) 		1
(1.00) 		0.393
(1.00) 		0.0355
(1.00) 		0.254
(1.00)
LCE1B 4 (9%) 41 0.443
(1.00) 		1
(1.00) 		0.608
(1.00) 		0.625
(1.00) 		0.949
(1.00)
MGAM 18 (40%) 27 0.623
(1.00) 		0.203
(1.00) 		0.387
(1.00) 		0.527
(1.00) 		0.96
(1.00) 		0.421
(1.00)
ACSM2B 6 (13%) 39 0.0265
(1.00) 		0.714
(1.00) 		0.595
(1.00) 		1
(1.00) 		0.832
(1.00) 		0.0425
(1.00)
'TP53 MUTATION STATUS' versus 'AGE'

P value = 0.000119 (t-test), Q value = 0.065

Table S1.  Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 45 57.8 (15.4)
TP53 MUTATED 9 73.1 (9.5)
TP53 WILD-TYPE 36 53.9 (14.2)

Figure S1.  Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'CLEC17A MUTATION STATUS' versus 'AGE'

P value = 4.55e-07 (t-test), Q value = 0.00025

Table S2.  Gene #48: 'CLEC17A MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 45 57.8 (15.4)
CLEC17A MUTATED 3 78.0 (2.6)
CLEC17A WILD-TYPE 42 56.3 (14.9)

Figure S2.  Get High-res Image Gene #48: 'CLEC17A MUTATION STATUS' versus Clinical Feature #2: 'AGE'

'OR4M2 MUTATION STATUS' versus 'AGE'

P value = 0.000255 (t-test), Q value = 0.14

Table S3.  Gene #95: 'OR4M2 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

nPatients Mean (Std.Dev)
ALL 45 57.8 (15.4)
OR4M2 MUTATED 6 73.7 (7.0)
OR4M2 WILD-TYPE 39 55.3 (14.9)

Figure S3.  Get High-res Image Gene #95: 'OR4M2 MUTATION STATUS' versus Clinical Feature #2: 'AGE'

Methods & Data
Input

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

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

  • Number of patients = 45

  • Number of significantly mutated genes = 99

  • Number of selected clinical features = 7

  • 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

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)
[5] 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)
Copyright © 2013 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle