Skin Cutaneous Melanoma: Correlation between gene mutation status and selected clinical features
(Regional_Metastatic 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 72 genes and 8 clinical features across 137 patients, 4 significant findings detected with Q value < 0.25.

  • OXA1L mutation correlated to 'LYMPH.NODE.METASTASIS'.

  • ACTL7B mutation correlated to 'LYMPH.NODE.METASTASIS'.

  • ANKRD20A4 mutation correlated to 'LYMPH.NODE.METASTASIS'.

  • VGLL1 mutation correlated to 'LYMPH.NODE.METASTASIS'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 72 genes and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 4 significant findings detected.

Clinical
Features 		Time
to
Death 		AGE PRIMARY
SITE
OF
DISEASE 		GENDER DISTANT
METASTASIS 		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 Chi-square test t-test Chi-square test
OXA1L 4 (3%) 133 0.509
(1.00) 		0.151
(1.00) 		0.573
(1.00) 		1
(1.00) 		0.996
(1.00) 		5.17e-05
(0.0258) 		0.294
(1.00)
ACTL7B 8 (6%) 129 0.352
(1.00) 		0.595
(1.00) 		0.681
(1.00) 		1
(1.00) 		0.994
(1.00) 		9.98e-08
(5e-05) 		0.0953
(1.00)
ANKRD20A4 4 (3%) 133 0.471
(1.00) 		0.529
(1.00) 		0.573
(1.00) 		0.3
(1.00) 		0.996
(1.00) 		0.000139
(0.0691) 		0.627
(1.00)
VGLL1 5 (4%) 132 0.983
(1.00) 		0.229
(1.00) 		0.332
(1.00) 		0.168
(1.00) 		0.996
(1.00) 		3.75e-05
(0.0187) 		0.929
(1.00)
CDKN2A 23 (17%) 114 0.585
(1.00) 		0.781
(1.00) 		0.42
(1.00) 		0.629
(1.00) 		0.9
(1.00) 		0.625
(1.00) 		0.749
(1.00)
TP53 23 (17%) 114 0.464
(1.00) 		0.0129
(1.00) 		1
(1.00) 		1
(1.00) 		0.918
(1.00) 		0.08
(1.00) 		0.223
(1.00)
BRAF 73 (53%) 64 0.683
(1.00) 		0.127
(1.00) 		0.232
(1.00) 		0.592
(1.00) 		0.608
(1.00) 		0.575
(1.00) 		0.521
(1.00)
C15ORF23 10 (7%) 127 0.85
(1.00) 		0.652
(1.00) 		0.698
(1.00) 		1
(1.00) 		0.982
(1.00) 		0.629
(1.00) 		0.602
(1.00)
ERVFRDE1 3 (2%) 134 0.00791
(1.00) 		0.685
(1.00) 		0.553
(1.00) 		0.551
(1.00)
NRAS 39 (28%) 98 0.85
(1.00) 		0.212
(1.00) 		0.823
(1.00) 		0.841
(1.00) 		0.795
(1.00) 		0.66
(1.00) 		0.523
(1.00)
PTEN 12 (9%) 125 0.642
(1.00) 		0.213
(1.00) 		0.294
(1.00) 		0.536
(1.00) 		0.0442
(1.00) 		0.845
(1.00) 		0.08
(1.00)
PPP6C 14 (10%) 123 0.0232
(1.00) 		0.721
(1.00) 		0.739
(1.00) 		1
(1.00) 		0.0785
(1.00) 		0.0621
(1.00) 		0.685
(1.00)
PRB4 16 (12%) 121 0.13
(1.00) 		0.0506
(1.00) 		0.117
(1.00) 		0.262
(1.00) 		0.956
(1.00) 		0.148
(1.00) 		0.907
(1.00)
RAC1 9 (7%) 128 0.498
(1.00) 		0.55
(1.00) 		1
(1.00) 		0.718
(1.00) 		0.989
(1.00) 		0.935
(1.00) 		0.499
(1.00)
CDH9 23 (17%) 114 0.201
(1.00) 		0.119
(1.00) 		0.0156
(1.00) 		0.812
(1.00) 		0.89
(1.00) 		0.267
(1.00) 		0.207
(1.00)
STK19 9 (7%) 128 0.524
(1.00) 		0.444
(1.00) 		1
(1.00) 		0.484
(1.00) 		0.986
(1.00) 		0.996
(1.00) 		0.927
(1.00)
ADH1C 20 (15%) 117 0.445
(1.00) 		0.286
(1.00) 		0.407
(1.00) 		0.451
(1.00) 		0.935
(1.00) 		0.117
(1.00) 		0.642
(1.00)
TCEB3C 19 (14%) 118 0.703
(1.00) 		0.611
(1.00) 		0.772
(1.00) 		0.115
(1.00) 		0.927
(1.00) 		0.478
(1.00) 		0.296
(1.00)
DDX3X 14 (10%) 123 0.252
(1.00) 		0.88
(1.00) 		0.315
(1.00) 		0.14
(1.00) 		0.00912
(1.00) 		0.993
(1.00) 		0.834
(1.00)
TRAT1 9 (7%) 128 0.0232
(1.00) 		0.232
(1.00) 		0.436
(1.00) 		1
(1.00) 		0.986
(1.00) 		0.0127
(1.00) 		0.917
(1.00)
TTN 108 (79%) 29 0.124
(1.00) 		0.805
(1.00) 		1
(1.00) 		0.185
(1.00) 		0.252
(1.00) 		0.209
(1.00) 		0.836
(1.00)
GH2 10 (7%) 127 0.574
(1.00) 		0.477
(1.00) 		0.698
(1.00) 		1
(1.00) 		0.986
(1.00) 		0.0136
(1.00) 		0.0294
(1.00)
TFEC 13 (9%) 124 0.337
(1.00) 		0.207
(1.00) 		1
(1.00) 		0.543
(1.00) 		0.968
(1.00) 		0.00767
(1.00) 		0.648
(1.00)
IDH1 7 (5%) 130 0.548
(1.00) 		0.0124
(1.00) 		1
(1.00) 		0.224
(1.00) 		0.989
(1.00) 		0.987
(1.00) 		0.582
(1.00)
WDR12 9 (7%) 128 0.887
(1.00) 		0.375
(1.00) 		1
(1.00) 		0.272
(1.00) 		0.989
(1.00) 		0.727
(1.00) 		0.951
(1.00)
RGS18 7 (5%) 130 0.853
(1.00) 		0.337
(1.00) 		0.354
(1.00) 		0.095
(1.00) 		0.992
(1.00) 		0.878
(1.00) 		0.82
(1.00)
POF1B 17 (12%) 120 0.298
(1.00) 		0.0388
(1.00) 		0.546
(1.00) 		0.79
(1.00) 		0.942
(1.00) 		0.169
(1.00) 		0.945
(1.00)
OR5AC2 16 (12%) 121 0.897
(1.00) 		0.813
(1.00) 		0.763
(1.00) 		1
(1.00) 		0.949
(1.00) 		0.706
(1.00) 		0.4
(1.00)
VEGFC 13 (9%) 124 0.358
(1.00) 		0.872
(1.00) 		0.299
(1.00) 		1
(1.00) 		0.968
(1.00) 		0.0184
(1.00) 		0.424
(1.00)
RERG 9 (7%) 128 0.712
(1.00) 		0.0934
(1.00) 		0.685
(1.00) 		0.718
(1.00) 		0.989
(1.00) 		0.00774
(1.00) 		0.519
(1.00)
CCNE2 10 (7%) 127 0.0237
(1.00) 		0.875
(1.00) 		0.116
(1.00) 		0.732
(1.00) 		0.978
(1.00) 		0.887
(1.00) 		0.492
(1.00)
GPR141 12 (9%) 125 0.663
(1.00) 		0.996
(1.00) 		0.474
(1.00) 		0.751
(1.00) 		0.968
(1.00) 		0.0775
(1.00) 		0.393
(1.00)
GK2 17 (12%) 120 0.336
(1.00) 		0.603
(1.00) 		0.228
(1.00) 		0.79
(1.00) 		0.949
(1.00) 		0.117
(1.00) 		0.26
(1.00)
NAP1L2 12 (9%) 125 0.827
(1.00) 		0.033
(1.00) 		0.732
(1.00) 		0.751
(1.00) 		0.968
(1.00) 		0.0523
(1.00) 		0.724
(1.00)
SNAP91 18 (13%) 119 0.877
(1.00) 		0.204
(1.00) 		0.565
(1.00) 		0.117
(1.00) 		0.607
(1.00) 		0.47
(1.00) 		0.587
(1.00)
PRB2 20 (15%) 117 0.751
(1.00) 		0.00623
(1.00) 		0.0436
(1.00) 		0.0732
(1.00) 		0.927
(1.00) 		0.361
(1.00) 		0.407
(1.00)
TLL1 27 (20%) 110 0.95
(1.00) 		0.125
(1.00) 		0.128
(1.00) 		0.181
(1.00) 		0.847
(1.00) 		0.0945
(1.00) 		0.122
(1.00)
HBD 8 (6%) 129 0.196
(1.00) 		0.809
(1.00) 		0.198
(1.00) 		1
(1.00) 		0.986
(1.00) 		0.98
(1.00) 		0.441
(1.00)
GRXCR2 11 (8%) 126 0.37
(1.00) 		0.694
(1.00) 		1
(1.00) 		0.751
(1.00) 		0.982
(1.00) 		0.0341
(1.00) 		0.554
(1.00)
NOTCH2NL 9 (7%) 128 0.924
(1.00) 		0.838
(1.00) 		0.213
(1.00) 		0.718
(1.00) 		0.986
(1.00) 		0.352
(1.00) 		0.442
(1.00)
AREG 6 (4%) 131 0.492
(1.00) 		0.293
(1.00) 		1
(1.00) 		0.403
(1.00) 		0.994
(1.00) 		0.00215
(1.00) 		0.527
(1.00)
HBG2 6 (4%) 131 0.252
(1.00) 		0.336
(1.00) 		0.624
(1.00) 		1
(1.00) 		0.992
(1.00) 		0.0069
(1.00) 		0.454
(1.00)
SERPINB4 20 (15%) 117 0.827
(1.00) 		0.283
(1.00) 		0.407
(1.00) 		0.0195
(1.00) 		0.201
(1.00) 		0.371
(1.00) 		0.939
(1.00)
SPTLC3 14 (10%) 123 0.303
(1.00) 		0.713
(1.00) 		0.188
(1.00) 		0.773
(1.00) 		0.956
(1.00) 		0.148
(1.00) 		0.232
(1.00)
TAF1A 9 (7%) 128 0.024
(1.00) 		0.884
(1.00) 		0.685
(1.00) 		0.484
(1.00) 		0.222
(1.00) 		0.737
(1.00) 		0.798
(1.00)
CLVS2 13 (9%) 124 0.666
(1.00) 		0.223
(1.00) 		0.732
(1.00) 		0.218
(1.00) 		0.968
(1.00) 		0.0794
(1.00) 		0.806
(1.00)
CCDC102B 15 (11%) 122 0.794
(1.00) 		0.486
(1.00) 		0.751
(1.00) 		0.773
(1.00) 		0.962
(1.00) 		0.115
(1.00) 		0.814
(1.00)
OR4N2 15 (11%) 122 0.859
(1.00) 		0.247
(1.00) 		0.751
(1.00) 		0.02
(1.00) 		0.0604
(1.00) 		0.26
(1.00) 		0.814
(1.00)
OR8D4 9 (7%) 128 0.0395
(1.00) 		0.62
(1.00) 		0.685
(1.00) 		1
(1.00) 		0.986
(1.00) 		0.0366
(1.00) 		0.98
(1.00)
RBM11 10 (7%) 127 0.836
(1.00) 		0.0147
(1.00) 		0.452
(1.00) 		0.495
(1.00) 		0.978
(1.00) 		0.0381
(1.00) 		0.434
(1.00)
DEFB118 7 (5%) 130 0.107
(1.00) 		0.64
(1.00) 		1
(1.00) 		1
(1.00) 		0.989
(1.00) 		0.0275
(1.00) 		0.781
(1.00)
GRXCR1 13 (9%) 124 0.332
(1.00) 		0.0168
(1.00) 		0.299
(1.00) 		1
(1.00) 		0.968
(1.00) 		0.845
(1.00) 		0.506
(1.00)
RGPD3 22 (16%) 115 0.981
(1.00) 		0.00584
(1.00) 		0.784
(1.00) 		0.0465
(1.00) 		0.705
(1.00) 		0.245
(1.00) 		0.863
(1.00)
CA1 8 (6%) 129 0.851
(1.00) 		0.881
(1.00) 		1
(1.00) 		0.267
(1.00) 		0.992
(1.00) 		0.891
(1.00) 		0.936
(1.00)
HNF4G 15 (11%) 122 0.0487
(1.00) 		0.114
(1.00) 		1
(1.00) 		0.385
(1.00) 		0.956
(1.00) 		0.012
(1.00) 		0.774
(1.00)
SPAG16 12 (9%) 125 0.658
(1.00) 		0.706
(1.00) 		1
(1.00) 		0.337
(1.00) 		0.978
(1.00) 		0.0759
(1.00) 		0.842
(1.00)
PCDHB8 23 (17%) 114 0.559
(1.00) 		0.498
(1.00) 		0.788
(1.00) 		0.231
(1.00) 		0.927
(1.00) 		0.377
(1.00) 		0.576
(1.00)
HIST1H2AA 5 (4%) 132 0.567
(1.00) 		0.822
(1.00) 		0.591
(1.00) 		1
(1.00) 		0.994
(1.00) 		0.963
(1.00) 		0.973
(1.00)
OR10K2 14 (10%) 123 0.148
(1.00) 		0.0061
(1.00) 		0.739
(1.00) 		0.14
(1.00) 		0.968
(1.00) 		0.174
(1.00) 		0.59
(1.00)
PHGDH 8 (6%) 129 0.722
(1.00) 		0.692
(1.00) 		0.681
(1.00) 		0.0514
(1.00) 		0.992
(1.00) 		0.00742
(1.00) 		0.116
(1.00)
OR9K2 11 (8%) 126 0.604
(1.00) 		0.0753
(1.00) 		0.067
(1.00) 		0.334
(1.00) 		0.973
(1.00) 		0.0952
(1.00) 		0.684
(1.00)
LIN7A 8 (6%) 129 0.875
(1.00) 		0.716
(1.00) 		0.198
(1.00) 		0.718
(1.00) 		0.992
(1.00) 		0.00897
(1.00) 		0.858
(1.00)
USP17L2 13 (9%) 124 0.751
(1.00) 		0.549
(1.00) 		0.182
(1.00) 		0.218
(1.00) 		0.968
(1.00) 		0.123
(1.00) 		0.251
(1.00)
CYLC2 14 (10%) 123 0.468
(1.00) 		0.171
(1.00) 		0.52
(1.00) 		0.14
(1.00) 		0.968
(1.00) 		0.0488
(1.00) 		0.735
(1.00)
DEFB110 5 (4%) 132 0.12
(1.00) 		0.994
(1.00) 		0.591
(1.00) 		0.168
(1.00) 		0.994
(1.00) 		0.000646
(0.32) 		0.671
(1.00)
LCE1B 7 (5%) 130 0.0484
(1.00) 		0.734
(1.00) 		0.665
(1.00) 		1
(1.00) 		0.992
(1.00) 		0.928
(1.00) 		0.864
(1.00)
PARM1 10 (7%) 127 0.228
(1.00) 		0.488
(1.00) 		0.698
(1.00) 		0.495
(1.00) 		0.982
(1.00) 		0.0267
(1.00) 		0.0858
(1.00)
ACSM2B 24 (18%) 113 0.406
(1.00) 		0.529
(1.00) 		0.195
(1.00) 		0.00368
(1.00) 		0.89
(1.00) 		0.413
(1.00) 		0.971
(1.00)
BAGE2 7 (5%) 130 0.737
(1.00) 		0.237
(1.00) 		0.2
(1.00) 		0.687
(1.00) 		0.000505
(0.251) 		0.00247
(1.00) 		0.207
(1.00)
CECR6 6 (4%) 131 0.338
(1.00) 		0.953
(1.00) 		1
(1.00) 		1
(1.00) 		0.992
(1.00) 		0.577
(1.00) 		0.553
(1.00)
OR4M2 15 (11%) 122 0.774
(1.00) 		0.000531
(0.263) 		0.52
(1.00) 		0.773
(1.00) 		0.956
(1.00) 		0.348
(1.00) 		0.228
(1.00)
CERKL 10 (7%) 127 0.62
(1.00) 		0.981
(1.00) 		0.698
(1.00) 		1
(1.00) 		0.982
(1.00) 		0.0547
(1.00) 		0.858
(1.00)
'OXA1L MUTATION STATUS' versus 'LYMPH.NODE.METASTASIS'

P value = 5.17e-05 (Chi-square test), Q value = 0.026

Table S1.  Gene #37: 'OXA1L MUTATION STATUS' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients N0 N1 N1A N1B N2 N2A N2B N2C N3 NX
ALL 71 2 6 11 1 4 10 4 15 1
OXA1L MUTATED 2 0 1 0 1 0 0 0 0 0
OXA1L WILD-TYPE 69 2 5 11 0 4 10 4 15 1

Figure S1.  Get High-res Image Gene #37: 'OXA1L MUTATION STATUS' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'ACTL7B MUTATION STATUS' versus 'LYMPH.NODE.METASTASIS'

P value = 9.98e-08 (Chi-square test), Q value = 5e-05

Table S2.  Gene #53: 'ACTL7B MUTATION STATUS' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients N0 N1 N1A N1B N2 N2A N2B N2C N3 NX
ALL 71 2 6 11 1 4 10 4 15 1
ACTL7B MUTATED 3 0 0 0 1 0 0 0 0 1
ACTL7B WILD-TYPE 68 2 6 11 0 4 10 4 15 0

Figure S2.  Get High-res Image Gene #53: 'ACTL7B MUTATION STATUS' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'ANKRD20A4 MUTATION STATUS' versus 'LYMPH.NODE.METASTASIS'

P value = 0.000139 (Chi-square test), Q value = 0.069

Table S3.  Gene #62: 'ANKRD20A4 MUTATION STATUS' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients N0 N1 N1A N1B N2 N2A N2B N2C N3 NX
ALL 71 2 6 11 1 4 10 4 15 1
ANKRD20A4 MUTATED 2 0 0 1 1 0 0 0 0 0
ANKRD20A4 WILD-TYPE 69 2 6 10 0 4 10 4 15 1

Figure S3.  Get High-res Image Gene #62: 'ANKRD20A4 MUTATION STATUS' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

'VGLL1 MUTATION STATUS' versus 'LYMPH.NODE.METASTASIS'

P value = 3.75e-05 (Chi-square test), Q value = 0.019

Table S4.  Gene #64: 'VGLL1 MUTATION STATUS' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

nPatients N0 N1 N1A N1B N2 N2A N2B N2C N3 NX
ALL 71 2 6 11 1 4 10 4 15 1
VGLL1 MUTATED 1 0 1 0 1 0 0 0 1 0
VGLL1 WILD-TYPE 70 2 5 11 0 4 10 4 14 1

Figure S4.  Get High-res Image Gene #64: 'VGLL1 MUTATION STATUS' versus Clinical Feature #6: 'LYMPH.NODE.METASTASIS'

Methods & Data
Input

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

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

  • Number of patients = 137

  • Number of significantly mutated genes = 72

  • 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

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)
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