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 84 genes and 8 clinical features across 512 patients, 29 significant findings detected with Q value < 0.25.

  • IDH1 mutation correlated to 'Time to Death',  'YEARS_TO_BIRTH',  'RADIATION_THERAPY',  'KARNOFSKY_PERFORMANCE_SCORE', and 'HISTOLOGICAL_TYPE'.

  • TP53 mutation correlated to 'YEARS_TO_BIRTH',  'RADIATION_THERAPY', and 'HISTOLOGICAL_TYPE'.

  • ATRX mutation correlated to 'YEARS_TO_BIRTH' and 'HISTOLOGICAL_TYPE'.

  • CIC mutation correlated to 'Time to Death',  'RADIATION_THERAPY', and 'HISTOLOGICAL_TYPE'.

  • NOTCH1 mutation correlated to 'HISTOLOGICAL_TYPE'.

  • IDH2 mutation correlated to 'HISTOLOGICAL_TYPE'.

  • FUBP1 mutation correlated to 'YEARS_TO_BIRTH' and 'HISTOLOGICAL_TYPE'.

  • NF1 mutation correlated to 'Time to Death'.

  • PTEN mutation correlated to 'Time to Death',  'YEARS_TO_BIRTH', and 'HISTOLOGICAL_TYPE'.

  • EGFR mutation correlated to 'Time to Death',  'YEARS_TO_BIRTH', and 'KARNOFSKY_PERFORMANCE_SCORE'.

  • SMARCA4 mutation correlated to 'Time to Death'.

  • SETD2 mutation correlated to 'YEARS_TO_BIRTH'.

  • HTR3A mutation correlated to 'RACE'.

  • WRN mutation correlated to 'ETHNICITY'.

  • TMEM184A mutation correlated to 'Time to Death'.

Results
Overview of the results

Table 1.  Get Full Table Overview of the association between mutation status of 84 genes and 8 clinical features. Shown in the table are P values (Q values). Thresholded by Q value < 0.25, 29 significant findings detected.

Clinical
Features 		Time
to
Death 		YEARS
TO
BIRTH 		GENDER RADIATION
THERAPY 		KARNOFSKY
PERFORMANCE
SCORE 		HISTOLOGICAL
TYPE 		RACE ETHNICITY
nMutated (%) nWild-Type logrank test Wilcoxon-test Fisher's exact test Fisher's exact test Wilcoxon-test Fisher's exact test Fisher's exact test Fisher's exact test
IDH1 397 (78%) 115 1.11e-16
(7.46e-14) 		9.38e-09
(1.05e-06) 		1
(1.00) 		0.00895
(0.215) 		0.00252
(0.0769) 		0.00513
(0.138) 		0.0253
(0.437) 		1
(1.00)
TP53 247 (48%) 265 0.054
(0.637) 		2.47e-12
(5.53e-10) 		0.286
(0.927) 		0.000168
(0.00708) 		0.279
(0.922) 		1e-05
(0.000611) 		0.0348
(0.557) 		0.715
(1.00)
CIC 108 (21%) 404 0.000136
(0.00608) 		0.107
(0.72) 		0.328
(0.93) 		3.46e-06
(0.000332) 		0.24
(0.888) 		1e-05
(0.000611) 		0.751
(1.00) 		0.656
(1.00)
PTEN 24 (5%) 488 0.00013
(0.00608) 		0.00176
(0.0623) 		0.297
(0.93) 		0.0671
(0.659) 		0.585
(1.00) 		0.00245
(0.0769) 		0.163
(0.787) 		1
(1.00)
EGFR 35 (7%) 477 1.23e-11
(2.07e-09) 		4.84e-11
(6.5e-09) 		1
(1.00) 		0.0148
(0.317) 		0.00495
(0.138) 		0.0484
(0.608) 		0.181
(0.81) 		0.718
(1.00)
ATRX 194 (38%) 318 0.0886
(0.659) 		1.97e-12
(5.53e-10) 		0.784
(1.00) 		0.0156
(0.317) 		0.797
(1.00) 		1e-05
(0.000611) 		0.436
(0.99) 		1
(1.00)
FUBP1 47 (9%) 465 0.13
(0.751) 		0.00301
(0.0881) 		0.645
(1.00) 		0.0695
(0.659) 		0.236
(0.888) 		1e-05
(0.000611) 		1
(1.00) 		0.1
(0.702)
NOTCH1 42 (8%) 470 0.12
(0.722) 		0.0424
(0.574) 		0.747
(1.00) 		0.392
(0.952) 		0.869
(1.00) 		5e-05
(0.0028) 		0.336
(0.931) 		1
(1.00)
IDH2 20 (4%) 492 0.0594
(0.655) 		0.074
(0.659) 		1
(1.00) 		0.477
(1.00) 		0.621
(1.00) 		0.00065
(0.0243) 		0.45
(0.999) 		0.127
(0.744)
NF1 33 (6%) 479 9.95e-05
(0.00514) 		0.0125
(0.28) 		0.59
(1.00) 		0.454
(1.00) 		0.549
(1.00) 		0.0155
(0.317) 		0.221
(0.883) 		0.258
(0.888)
SMARCA4 26 (5%) 486 0.00715
(0.185) 		0.523
(1.00) 		0.318
(0.93) 		1
(1.00) 		0.432
(0.984) 		0.79
(1.00) 		0.115
(0.72) 		0.644
(1.00)
SETD2 10 (2%) 502 0.56
(1.00) 		0.00794
(0.198) 		1
(1.00) 		0.747
(1.00) 		0.308
(0.93) 		0.362
(0.944) 		0.466
(1.00) 		1
(1.00)
HTR3A 7 (1%) 505 0.403
(0.952) 		0.54
(1.00) 		0.0489
(0.608) 		0.439
(0.99) 		0.0794
(0.659) 		0.9
(1.00) 		0.00927
(0.215) 		1
(1.00)
WRN 5 (1%) 507 0.0842
(0.659) 		0.381
(0.948) 		0.661
(1.00) 		1
(1.00) 		0.0379
(0.559) 		0.552
(1.00) 		0.266
(0.899) 		0.0025
(0.0769)
TMEM184A 3 (1%) 509 0.000525
(0.0207) 		0.151
(0.787) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.17
(0.787) 		1
(1.00)
PIK3R1 22 (4%) 490 0.259
(0.888) 		0.0799
(0.659) 		0.275
(0.913) 		0.487
(1.00) 		0.522
(1.00) 		0.354
(0.931) 		0.0455
(0.598) 		0.623
(1.00)
ARID1A 20 (4%) 492 0.0379
(0.559) 		0.648
(1.00) 		0.493
(1.00) 		0.351
(0.931) 		0.964
(1.00) 		0.195
(0.836) 		1
(1.00) 		1
(1.00)
GAGE2A 8 (2%) 504 0.507
(1.00) 		0.733
(1.00) 		0.737
(1.00) 		1
(1.00) 		0.323
(0.93) 		1
(1.00) 		0.054
(0.637) 		0.428
(0.978)
NUDT11 11 (2%) 501 0.525
(1.00) 		0.321
(0.93) 		0.36
(0.941) 		1
(1.00) 		0.641
(1.00) 		0.745
(1.00) 		1
(1.00) 		1
(1.00)
PIK3CA 44 (9%) 468 0.65
(1.00) 		0.0729
(0.659) 		0.875
(1.00) 		0.256
(0.888) 		0.102
(0.705) 		0.0182
(0.34) 		0.628
(1.00) 		0.743
(1.00)
STK19 10 (2%) 502 0.307
(0.93) 		0.311
(0.93) 		0.12
(0.722) 		0.682
(1.00) 		0.23
(0.888) 		0.0754
(0.659) 		1
(1.00) 		0.14
(0.769)
EMG1 6 (1%) 506 0.537
(1.00) 		0.0981
(0.694) 		0.415
(0.952) 		1
(1.00) 		0.366
(0.948) 		0.351
(0.931) 		1
(1.00) 		1
(1.00)
NIPBL 18 (4%) 494 0.0578
(0.654) 		0.176
(0.803) 		0.156
(0.787) 		0.311
(0.93) 		0.604
(1.00) 		0.0697
(0.659) 		0.0756
(0.659) 		0.112
(0.72)
TCF12 15 (3%) 497 0.625
(1.00) 		0.225
(0.888) 		0.601
(1.00) 		1
(1.00) 		0.915
(1.00) 		0.895
(1.00) 		1
(1.00) 		0.613
(1.00)
DNMT3A 10 (2%) 502 0.0364
(0.559) 		0.479
(1.00) 		1
(1.00) 		0.747
(1.00) 		0.992
(1.00) 		0.337
(0.931) 		0.462
(1.00) 		0.503
(1.00)
TRERF1 6 (1%) 506 0.482
(1.00) 		0.285
(0.927) 		0.0941
(0.672) 		0.682
(1.00) 		0.798
(1.00) 		0.167
(0.787) 		1
(1.00) 		1
(1.00)
CREBZF 7 (1%) 505 0.955
(1.00) 		0.171
(0.787) 		0.251
(0.888) 		1
(1.00) 		0.0699
(0.659) 		0.0314
(0.515) 		0.35
(0.931) 		0.386
(0.948)
FAM47C 18 (4%) 494 0.0775
(0.659) 		0.562
(1.00) 		0.47
(1.00) 		0.46
(1.00) 		0.649
(1.00) 		0.595
(1.00) 		1
(1.00) 		1
(1.00)
MYST4 11 (2%) 501 0.0922
(0.666) 		0.108
(0.72) 		1
(1.00) 		1
(1.00) 		0.928
(1.00) 		0.189
(0.831) 		0.147
(0.787) 		0.503
(1.00)
MED9 3 (1%) 509 0.23
(0.888) 		0.871
(1.00) 		0.257
(0.888) 		0.285
(0.927) 		0.0162
(0.32) 		1
(1.00) 		1
(1.00)
IRS4 7 (1%) 505 0.16
(0.787) 		0.495
(1.00) 		1
(1.00) 		1
(1.00) 		0.664
(1.00) 		0.137
(0.769) 		1
(1.00) 		0.386
(0.948)
HTRA2 5 (1%) 507 0.339
(0.931) 		0.0279
(0.469) 		1
(1.00) 		0.39
(0.952) 		0.451
(0.999) 		1
(1.00) 		0.294
(0.927)
NRAS 4 (1%) 508 0.28
(0.922) 		0.883
(1.00) 		1
(1.00) 		0.645
(1.00) 		0.471
(1.00) 		0.023
(0.406) 		1
(1.00) 		1
(1.00)
TNRC18 9 (2%) 503 0.321
(0.93) 		0.948
(1.00) 		0.198
(0.841) 		0.493
(1.00) 		0.915
(1.00) 		0.151
(0.787) 		1
(1.00) 		1
(1.00)
ZNF709 4 (1%) 508 0.0842
(0.659) 		0.595
(1.00) 		0.132
(0.751) 		1
(1.00) 		0.139
(0.769) 		0.22
(0.883) 		0.243
(0.888)
PLXNA3 9 (2%) 503 0.0907
(0.663) 		0.249
(0.888) 		0.311
(0.93) 		0.158
(0.787) 		0.588
(1.00) 		0.834
(1.00) 		0.109
(0.72) 		1
(1.00)
ROBO3 5 (1%) 507 0.49
(1.00) 		0.533
(1.00) 		0.661
(1.00) 		0.645
(1.00) 		0.664
(1.00) 		0.378
(0.948) 		1
(1.00) 		0.294
(0.927)
RB1 6 (1%) 506 0.829
(1.00) 		0.165
(0.787) 		0.415
(0.952) 		1
(1.00) 		0.0807
(0.659) 		0.315
(0.93) 		1
(1.00)
SRPX 4 (1%) 508 0.151
(0.787) 		0.0427
(0.574) 		0.0394
(0.561) 		1
(1.00) 		0.555
(1.00) 		0.377
(0.948) 		0.22
(0.883) 		1
(1.00)
PDGFRA 10 (2%) 502 0.0741
(0.659) 		0.707
(1.00) 		0.354
(0.931) 		0.747
(1.00) 		0.142
(0.775) 		0.115
(0.72) 		1
(1.00) 		0.14
(0.769)
ZNF512B 5 (1%) 507 0.08
(0.659) 		0.301
(0.93) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.294
(0.927)
ZMIZ1 9 (2%) 503 0.0712
(0.659) 		0.862
(1.00) 		0.522
(1.00) 		1
(1.00) 		0.149
(0.787) 		0.44
(0.99) 		0.0661
(0.659) 		0.0174
(0.334)
TMEM216 3 (1%) 509 0.771
(1.00) 		0.817
(1.00) 		0.0888
(0.659) 		1
(1.00) 		0.367
(0.948) 		1
(1.00) 		1
(1.00)
ARID2 11 (2%) 501 0.51
(1.00) 		0.109
(0.72) 		1
(1.00) 		0.215
(0.883) 		0.807
(1.00) 		0.206
(0.864) 		0.244
(0.888) 		1
(1.00)
RBPJ 7 (1%) 505 0.873
(1.00) 		0.0538
(0.637) 		1
(1.00) 		0.682
(1.00) 		0.335
(0.931) 		0.274
(0.913) 		1
(1.00) 		1
(1.00)
CUL4B 10 (2%) 502 0.211
(0.882) 		0.824
(1.00) 		0.12
(0.722) 		0.329
(0.93) 		0.641
(1.00) 		0.335
(0.931) 		0.219
(0.883) 		1
(1.00)
SLC6A3 9 (2%) 503 0.642
(1.00) 		0.377
(0.948) 		0.522
(1.00) 		1
(1.00) 		0.761
(1.00) 		1
(1.00) 		0.386
(0.948)
KRT3 4 (1%) 508 0.0883
(0.659) 		0.856
(1.00) 		0.632
(1.00) 		1
(1.00) 		0.105
(0.72) 		0.684
(1.00) 		1
(1.00) 		0.243
(0.888)
MYT1 6 (1%) 506 0.268
(0.899) 		0.408
(0.952) 		1
(1.00) 		0.0861
(0.659) 		0.734
(1.00) 		0.17
(0.787) 		1
(1.00) 		1
(1.00)
SMOC1 3 (1%) 509 0.489
(1.00) 		0.443
(0.993) 		1
(1.00) 		0.523
(1.00) 		0.978
(1.00) 		0.475
(1.00) 		1
(1.00) 		1
(1.00)
ZBTB20 21 (4%) 491 0.229
(0.888) 		0.495
(1.00) 		0.371
(0.948) 		0.161
(0.787) 		0.798
(1.00) 		0.182
(0.81) 		0.127
(0.744) 		0.636
(1.00)
PPL 6 (1%) 506 0.0401
(0.561) 		0.727
(1.00) 		1
(1.00) 		1
(1.00) 		0.798
(1.00) 		0.401
(0.952) 		1
(1.00) 		0.294
(0.927)
PTPN11 7 (1%) 505 0.253
(0.888) 		0.342
(0.931) 		1
(1.00) 		1
(1.00) 		0.755
(1.00) 		0.309
(0.93) 		0.354
(0.931) 		1
(1.00)
RET 7 (1%) 505 0.651
(1.00) 		0.5
(1.00) 		0.251
(0.888) 		0.439
(0.99) 		0.6
(1.00) 		0.0724
(0.659) 		1
(1.00) 		1
(1.00)
ANKRD36 7 (1%) 505 0.0892
(0.659) 		0.593
(1.00) 		0.706
(1.00) 		0.0463
(0.598) 		0.0699
(0.659) 		0.237
(0.888) 		0.0698
(0.659) 		1
(1.00)
NEU2 5 (1%) 507 0.227
(0.888) 		0.168
(0.787) 		1
(1.00) 		1
(1.00) 		0.38
(0.948) 		1
(1.00) 		0.294
(0.927)
PRX 10 (2%) 502 0.761
(1.00) 		0.463
(1.00) 		0.354
(0.931) 		0.329
(0.93) 		0.33
(0.93) 		0.781
(1.00) 		1
(1.00) 		0.503
(1.00)
RBBP6 6 (1%) 506 0.195
(0.836) 		0.321
(0.93) 		1
(1.00) 		0.682
(1.00) 		0.773
(1.00) 		0.125
(0.74) 		1
(1.00)
CIB1 4 (1%) 508 0.407
(0.952) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.755
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
DDX5 5 (1%) 507 0.114
(0.72) 		0.854
(1.00) 		1
(1.00) 		1
(1.00) 		0.289
(0.927) 		0.852
(1.00) 		1
(1.00) 		0.243
(0.888)
NAP1L2 4 (1%) 508 0.267
(0.899) 		0.178
(0.803) 		1
(1.00) 		0.645
(1.00) 		0.195
(0.836) 		1
(1.00) 		1
(1.00)
SCN4A 6 (1%) 506 0.187
(0.827) 		0.26
(0.888) 		0.415
(0.952) 		0.682
(1.00) 		0.333
(0.931) 		0.775
(1.00) 		1
(1.00) 		1
(1.00)
AGBL1 5 (1%) 507 0.254
(0.888) 		0.203
(0.856) 		0.386
(0.948) 		1
(1.00) 		0.192
(0.836) 		1
(1.00) 		1
(1.00)
TPX2 5 (1%) 507 0.233
(0.888) 		0.983
(1.00) 		0.661
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		0.0383
(0.559)
KRT15 6 (1%) 506 0.751
(1.00) 		0.116
(0.72) 		0.696
(1.00) 		0.215
(0.883) 		0.41
(0.952) 		0.886
(1.00) 		0.313
(0.93) 		1
(1.00)
C14ORF4 3 (1%) 509 0.467
(1.00) 		0.739
(1.00) 		0.589
(1.00) 		1
(1.00) 		0.786
(1.00) 		0.17
(0.787) 		1
(1.00)
R3HDM1 7 (1%) 505 0.0584
(0.654) 		0.872
(1.00) 		1
(1.00) 		1
(1.00) 		0.755
(1.00) 		0.494
(1.00) 		1
(1.00) 		0.386
(0.948)
G6PC 6 (1%) 506 0.878
(1.00) 		0.401
(0.952) 		0.696
(1.00) 		0.412
(0.952) 		0.51
(1.00) 		0.403
(0.952) 		1
(1.00) 		0.055
(0.638)
DLC1 6 (1%) 506 0.561
(1.00) 		0.553
(1.00) 		0.415
(0.952) 		0.0861
(0.659) 		0.666
(1.00) 		1
(1.00) 		0.342
(0.931)
SLC12A7 7 (1%) 505 0.178
(0.803) 		0.54
(1.00) 		0.706
(1.00) 		0.412
(0.952) 		0.52
(1.00) 		1
(1.00) 		0.35
(0.931) 		1
(1.00)
SMARCB1 4 (1%) 508 0.312
(0.93) 		0.811
(1.00) 		0.632
(1.00) 		0.16
(0.787) 		0.755
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
LAMA4 4 (1%) 508 0.796
(1.00) 		0.354
(0.931) 		0.132
(0.751) 		1
(1.00) 		0.755
(1.00) 		0.0667
(0.659) 		0.0795
(0.659) 		0.243
(0.888)
MAST2 5 (1%) 507 0.472
(1.00) 		0.705
(1.00) 		0.661
(1.00) 		0.162
(0.787) 		0.45
(0.999) 		1
(1.00) 		1
(1.00)
ZMYM2 7 (1%) 505 0.153
(0.787) 		0.7
(1.00) 		1
(1.00) 		0.255
(0.888) 		0.664
(1.00) 		1
(1.00) 		1
(1.00) 		0.386
(0.948)
SLFN11 4 (1%) 508 0.114
(0.72) 		0.0862
(0.659) 		0.632
(1.00) 		0.645
(1.00) 		0.567
(1.00) 		1
(1.00) 		0.243
(0.888)
C4BPA 6 (1%) 506 0.528
(1.00) 		0.64
(1.00) 		0.415
(0.952) 		0.412
(0.952) 		0.166
(0.787) 		0.885
(1.00) 		0.307
(0.93) 		0.342
(0.931)
KTELC1 5 (1%) 507 0.312
(0.93) 		0.66
(1.00) 		0.386
(0.948) 		0.653
(1.00) 		0.852
(1.00) 		1
(1.00) 		1
(1.00)
ASXL2 3 (1%) 509 0.12
(0.722) 		0.413
(0.952) 		0.589
(1.00) 		1
(1.00) 		0.627
(1.00) 		1
(1.00) 		1
(1.00)
CCDC135 7 (1%) 505 0.236
(0.888) 		0.757
(1.00) 		0.251
(0.888) 		1
(1.00) 		0.706
(1.00) 		1
(1.00) 		0.386
(0.948)
SLC25A5 4 (1%) 508 0.0229
(0.406) 		0.579
(1.00) 		0.329
(0.93) 		1
(1.00) 		0.25
(0.888) 		0.837
(1.00) 		0.221
(0.883) 		1
(1.00)
ABCA7 9 (2%) 503 0.752
(1.00) 		0.163
(0.787) 		0.738
(1.00) 		1
(1.00) 		0.559
(1.00) 		0.534
(1.00) 		1
(1.00) 		1
(1.00)
NKD2 4 (1%) 508 0.989
(1.00) 		0.687
(1.00) 		1
(1.00) 		0.304
(0.93) 		0.456
(1.00) 		1
(1.00) 		1
(1.00)
MAX 4 (1%) 508 0.801
(1.00) 		0.166
(0.787) 		0.329
(0.93) 		0.563
(1.00) 		0.978
(1.00) 		0.838
(1.00) 		1
(1.00) 		1
(1.00)
VSIG4 6 (1%) 506 0.915
(1.00) 		0.946
(1.00) 		0.415
(0.952) 		1
(1.00) 		1
(1.00) 		1
(1.00) 		1
(1.00)
'IDH1 MUTATION STATUS' versus 'Time to Death'

P value = 1.11e-16 (logrank test), Q value = 7.5e-14

Table S1.  Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 509 119 0.0 - 211.2 (20.7)
IDH1 MUTATED 394 68 0.0 - 182.3 (23.3)
IDH1 WILD-TYPE 115 51 0.1 - 211.2 (16.2)

Figure S1.  Get High-res Image Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'IDH1 MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 9.38e-09 (Wilcoxon-test), Q value = 1.1e-06

Table S2.  Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 511 42.9 (13.4)
IDH1 MUTATED 396 41.0 (12.4)
IDH1 WILD-TYPE 115 49.6 (14.6)

Figure S2.  Get High-res Image Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'IDH1 MUTATION STATUS' versus 'RADIATION_THERAPY'

P value = 0.00895 (Fisher's exact test), Q value = 0.21

Table S3.  Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #4: 'RADIATION_THERAPY'

nPatients NO YES
ALL 186 291
IDH1 MUTATED 157 216
IDH1 WILD-TYPE 29 75

Figure S3.  Get High-res Image Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #4: 'RADIATION_THERAPY'

'IDH1 MUTATION STATUS' versus 'KARNOFSKY_PERFORMANCE_SCORE'

P value = 0.00252 (Wilcoxon-test), Q value = 0.077

Table S4.  Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #5: 'KARNOFSKY_PERFORMANCE_SCORE'

nPatients Mean (Std.Dev)
ALL 306 86.7 (12.4)
IDH1 MUTATED 240 87.8 (11.8)
IDH1 WILD-TYPE 66 82.7 (13.8)

Figure S4.  Get High-res Image Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #5: 'KARNOFSKY_PERFORMANCE_SCORE'

'IDH1 MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 0.00513 (Fisher's exact test), Q value = 0.14

Table S5.  Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 192 130 190
IDH1 MUTATED 134 109 154
IDH1 WILD-TYPE 58 21 36

Figure S5.  Get High-res Image Gene #1: 'IDH1 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'TP53 MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 2.47e-12 (Wilcoxon-test), Q value = 5.5e-10

Table S6.  Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 511 42.9 (13.4)
TP53 MUTATED 247 38.6 (11.3)
TP53 WILD-TYPE 264 47.0 (13.9)

Figure S6.  Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'TP53 MUTATION STATUS' versus 'RADIATION_THERAPY'

P value = 0.000168 (Fisher's exact test), Q value = 0.0071

Table S7.  Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #4: 'RADIATION_THERAPY'

nPatients NO YES
ALL 186 291
TP53 MUTATED 71 163
TP53 WILD-TYPE 115 128

Figure S7.  Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #4: 'RADIATION_THERAPY'

'TP53 MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.00061

Table S8.  Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 192 130 190
TP53 MUTATED 129 74 44
TP53 WILD-TYPE 63 56 146

Figure S8.  Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'ATRX MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 1.97e-12 (Wilcoxon-test), Q value = 5.5e-10

Table S9.  Gene #3: 'ATRX MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 511 42.9 (13.4)
ATRX MUTATED 194 37.8 (11.9)
ATRX WILD-TYPE 317 46.1 (13.3)

Figure S9.  Get High-res Image Gene #3: 'ATRX MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'ATRX MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.00061

Table S10.  Gene #3: 'ATRX MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 192 130 190
ATRX MUTATED 96 64 34
ATRX WILD-TYPE 96 66 156

Figure S10.  Get High-res Image Gene #3: 'ATRX MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'CIC MUTATION STATUS' versus 'Time to Death'

P value = 0.000136 (logrank test), Q value = 0.0061

Table S11.  Gene #4: 'CIC MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 509 119 0.0 - 211.2 (20.7)
CIC MUTATED 107 12 0.1 - 211.2 (23.2)
CIC WILD-TYPE 402 107 0.0 - 172.8 (20.1)

Figure S11.  Get High-res Image Gene #4: 'CIC MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'CIC MUTATION STATUS' versus 'RADIATION_THERAPY'

P value = 3.46e-06 (Fisher's exact test), Q value = 0.00033

Table S12.  Gene #4: 'CIC MUTATION STATUS' versus Clinical Feature #4: 'RADIATION_THERAPY'

nPatients NO YES
ALL 186 291
CIC MUTATED 60 41
CIC WILD-TYPE 126 250

Figure S12.  Get High-res Image Gene #4: 'CIC MUTATION STATUS' versus Clinical Feature #4: 'RADIATION_THERAPY'

'CIC MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.00061

Table S13.  Gene #4: 'CIC MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 192 130 190
CIC MUTATED 3 23 82
CIC WILD-TYPE 189 107 108

Figure S13.  Get High-res Image Gene #4: 'CIC MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'NOTCH1 MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 5e-05 (Fisher's exact test), Q value = 0.0028

Table S14.  Gene #5: 'NOTCH1 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 192 130 190
NOTCH1 MUTATED 6 7 29
NOTCH1 WILD-TYPE 186 123 161

Figure S14.  Get High-res Image Gene #5: 'NOTCH1 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'IDH2 MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 0.00065 (Fisher's exact test), Q value = 0.024

Table S15.  Gene #6: 'IDH2 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 192 130 190
IDH2 MUTATED 1 5 14
IDH2 WILD-TYPE 191 125 176

Figure S15.  Get High-res Image Gene #6: 'IDH2 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'FUBP1 MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 0.00301 (Wilcoxon-test), Q value = 0.088

Table S16.  Gene #8: 'FUBP1 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 511 42.9 (13.4)
FUBP1 MUTATED 47 47.4 (9.5)
FUBP1 WILD-TYPE 464 42.5 (13.6)

Figure S16.  Get High-res Image Gene #8: 'FUBP1 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'FUBP1 MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 1e-05 (Fisher's exact test), Q value = 0.00061

Table S17.  Gene #8: 'FUBP1 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 192 130 190
FUBP1 MUTATED 2 9 36
FUBP1 WILD-TYPE 190 121 154

Figure S17.  Get High-res Image Gene #8: 'FUBP1 MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'NF1 MUTATION STATUS' versus 'Time to Death'

P value = 9.95e-05 (logrank test), Q value = 0.0051

Table S18.  Gene #9: 'NF1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 509 119 0.0 - 211.2 (20.7)
NF1 MUTATED 33 15 0.2 - 211.2 (18.6)
NF1 WILD-TYPE 476 104 0.0 - 182.3 (21.3)

Figure S18.  Get High-res Image Gene #9: 'NF1 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'PTEN MUTATION STATUS' versus 'Time to Death'

P value = 0.00013 (logrank test), Q value = 0.0061

Table S19.  Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 509 119 0.0 - 211.2 (20.7)
PTEN MUTATED 24 12 0.5 - 211.2 (17.1)
PTEN WILD-TYPE 485 107 0.0 - 182.3 (21.3)

Figure S19.  Get High-res Image Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'PTEN MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 0.00176 (Wilcoxon-test), Q value = 0.062

Table S20.  Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 511 42.9 (13.4)
PTEN MUTATED 24 51.0 (12.0)
PTEN WILD-TYPE 487 42.5 (13.3)

Figure S20.  Get High-res Image Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'PTEN MUTATION STATUS' versus 'HISTOLOGICAL_TYPE'

P value = 0.00245 (Fisher's exact test), Q value = 0.077

Table S21.  Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

nPatients ASTROCYTOMA OLIGOASTROCYTOMA OLIGODENDROGLIOMA
ALL 192 130 190
PTEN MUTATED 17 4 3
PTEN WILD-TYPE 175 126 187

Figure S21.  Get High-res Image Gene #11: 'PTEN MUTATION STATUS' versus Clinical Feature #6: 'HISTOLOGICAL_TYPE'

'EGFR MUTATION STATUS' versus 'Time to Death'

P value = 1.23e-11 (logrank test), Q value = 2.1e-09

Table S22.  Gene #12: 'EGFR MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 509 119 0.0 - 211.2 (20.7)
EGFR MUTATED 35 21 0.5 - 211.2 (13.1)
EGFR WILD-TYPE 474 98 0.0 - 182.3 (21.5)

Figure S22.  Get High-res Image Gene #12: 'EGFR MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'EGFR MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 4.84e-11 (Wilcoxon-test), Q value = 6.5e-09

Table S23.  Gene #12: 'EGFR MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 511 42.9 (13.4)
EGFR MUTATED 35 57.7 (9.1)
EGFR WILD-TYPE 476 41.8 (13.0)

Figure S23.  Get High-res Image Gene #12: 'EGFR MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'EGFR MUTATION STATUS' versus 'KARNOFSKY_PERFORMANCE_SCORE'

P value = 0.00495 (Wilcoxon-test), Q value = 0.14

Table S24.  Gene #12: 'EGFR MUTATION STATUS' versus Clinical Feature #5: 'KARNOFSKY_PERFORMANCE_SCORE'

nPatients Mean (Std.Dev)
ALL 306 86.7 (12.4)
EGFR MUTATED 22 78.2 (16.8)
EGFR WILD-TYPE 284 87.4 (11.8)

Figure S24.  Get High-res Image Gene #12: 'EGFR MUTATION STATUS' versus Clinical Feature #5: 'KARNOFSKY_PERFORMANCE_SCORE'

'SMARCA4 MUTATION STATUS' versus 'Time to Death'

P value = 0.00715 (logrank test), Q value = 0.18

Table S25.  Gene #18: 'SMARCA4 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 509 119 0.0 - 211.2 (20.7)
SMARCA4 MUTATED 26 1 0.2 - 211.2 (27.2)
SMARCA4 WILD-TYPE 483 118 0.0 - 182.3 (20.7)

Figure S25.  Get High-res Image Gene #18: 'SMARCA4 MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

'SETD2 MUTATION STATUS' versus 'YEARS_TO_BIRTH'

P value = 0.00794 (Wilcoxon-test), Q value = 0.2

Table S26.  Gene #44: 'SETD2 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

nPatients Mean (Std.Dev)
ALL 511 42.9 (13.4)
SETD2 MUTATED 10 54.0 (10.9)
SETD2 WILD-TYPE 501 42.7 (13.3)

Figure S26.  Get High-res Image Gene #44: 'SETD2 MUTATION STATUS' versus Clinical Feature #2: 'YEARS_TO_BIRTH'

'HTR3A MUTATION STATUS' versus 'RACE'

P value = 0.00927 (Fisher's exact test), Q value = 0.21

Table S27.  Gene #63: 'HTR3A MUTATION STATUS' versus Clinical Feature #7: 'RACE'

nPatients AMERICAN INDIAN OR ALASKA NATIVE ASIAN BLACK OR AFRICAN AMERICAN WHITE
ALL 1 8 21 472
HTR3A MUTATED 0 2 0 4
HTR3A WILD-TYPE 1 6 21 468

Figure S27.  Get High-res Image Gene #63: 'HTR3A MUTATION STATUS' versus Clinical Feature #7: 'RACE'

'WRN MUTATION STATUS' versus 'ETHNICITY'

P value = 0.0025 (Fisher's exact test), Q value = 0.077

Table S28.  Gene #70: 'WRN MUTATION STATUS' versus Clinical Feature #8: 'ETHNICITY'

nPatients HISPANIC OR LATINO NOT HISPANIC OR LATINO
ALL 32 446
WRN MUTATED 3 2
WRN WILD-TYPE 29 444

Figure S28.  Get High-res Image Gene #70: 'WRN MUTATION STATUS' versus Clinical Feature #8: 'ETHNICITY'

'TMEM184A MUTATION STATUS' versus 'Time to Death'

P value = 0.000525 (logrank test), Q value = 0.021

Table S29.  Gene #76: 'TMEM184A MUTATION STATUS' versus Clinical Feature #1: 'Time to Death'

nPatients nDeath Duration Range (Median), Month
ALL 509 119 0.0 - 211.2 (20.7)
TMEM184A MUTATED 3 1 0.3 - 9.2 (6.5)
TMEM184A WILD-TYPE 506 118 0.0 - 211.2 (20.8)

Figure S29.  Get High-res Image Gene #76: 'TMEM184A 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/LGG-TP/20067756/transformed.cor.cli.txt

  • Clinical data file = /xchip/cga/gdac-prod/tcga-gdac/jobResults/Append_Data/LGG-TP/19775312/LGG-TP.merged_data.txt

  • Number of patients = 512

  • Number of significantly mutated genes = 84

  • 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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