This pipeline computes the correlation between significantly recurrent gene mutations and molecular subtypes.
Testing the association between mutation status of 45 genes and 10 molecular subtypes across 306 patients, 19 significant findings detected with P value < 0.05 and Q value < 0.25.
-
NSD1 mutation correlated to 'METHLYATION_CNMF', 'MRNASEQ_CNMF', and 'MRNASEQ_CHIERARCHICAL'.
-
HRAS mutation correlated to 'CN_CNMF'.
-
TP53 mutation correlated to 'CN_CNMF'.
-
NOTCH1 mutation correlated to 'METHLYATION_CNMF', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', and 'MIRSEQ_CNMF'.
-
CASP8 mutation correlated to 'CN_CNMF', 'METHLYATION_CNMF', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', and 'MIRSEQ_MATURE_CNMF'.
-
EPHA2 mutation correlated to 'MIRSEQ_MATURE_CNMF'.
-
CSMD3 mutation correlated to 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', 'MIRSEQ_CNMF', and 'MIRSEQ_MATURE_CNMF'.
Clinical Features |
CN CNMF |
METHLYATION CNMF |
RPPA CNMF |
RPPA CHIERARCHICAL |
MRNASEQ CNMF |
MRNASEQ CHIERARCHICAL |
MIRSEQ CNMF |
MIRSEQ CHIERARCHICAL |
MIRSEQ MATURE CNMF |
MIRSEQ MATURE CHIERARCHICAL |
||
nMutated (%) | nWild-Type | Chi-square 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 | Fisher's exact test | Fisher's exact test | Fisher's exact test | |
CASP8 | 27 (9%) | 279 |
1.62e-05 (0.00695) |
0.000335 (0.142) |
0.699 (1.00) |
0.739 (1.00) |
3e-07 (0.000131) |
5.28e-07 (0.00023) |
0.377 (1.00) |
0.564 (1.00) |
0.000302 (0.128) |
0.0244 (1.00) |
NOTCH1 | 57 (19%) | 249 |
0.88 (1.00) |
0.000562 (0.236) |
0.0187 (1.00) |
0.279 (1.00) |
0.000428 (0.181) |
2.54e-06 (0.0011) |
0.000112 (0.0481) |
0.292 (1.00) |
0.000786 (0.329) |
0.0017 (0.703) |
CSMD3 | 70 (23%) | 236 |
0.0549 (1.00) |
0.00234 (0.965) |
0.00973 (1.00) |
0.463 (1.00) |
1.35e-05 (0.00583) |
6.66e-07 (0.00029) |
0.000542 (0.228) |
0.00103 (0.429) |
0.000137 (0.0586) |
0.00299 (1.00) |
NSD1 | 33 (11%) | 273 |
0.302 (1.00) |
1.27e-05 (0.0055) |
0.244 (1.00) |
0.73 (1.00) |
0.000411 (0.174) |
6.41e-06 (0.00277) |
0.00974 (1.00) |
0.0355 (1.00) |
0.0297 (1.00) |
0.0072 (1.00) |
HRAS | 10 (3%) | 296 |
8.17e-05 (0.0351) |
0.0261 (1.00) |
0.168 (1.00) |
0.599 (1.00) |
0.00339 (1.00) |
0.0011 (0.457) |
0.0991 (1.00) |
0.188 (1.00) |
0.0484 (1.00) |
0.21 (1.00) |
TP53 | 214 (70%) | 92 |
1.7e-12 (7.44e-10) |
0.00948 (1.00) |
0.11 (1.00) |
0.776 (1.00) |
0.0113 (1.00) |
0.00143 (0.592) |
0.0611 (1.00) |
0.0008 (0.334) |
0.0417 (1.00) |
0.00811 (1.00) |
EPHA2 | 14 (5%) | 292 |
0.111 (1.00) |
0.00794 (1.00) |
0.811 (1.00) |
0.906 (1.00) |
0.499 (1.00) |
0.57 (1.00) |
0.775 (1.00) |
0.184 (1.00) |
0.000357 (0.151) |
0.0592 (1.00) |
PIK3CA | 64 (21%) | 242 |
0.0654 (1.00) |
0.0334 (1.00) |
0.0948 (1.00) |
0.928 (1.00) |
0.119 (1.00) |
0.398 (1.00) |
0.038 (1.00) |
0.0446 (1.00) |
0.0942 (1.00) |
0.304 (1.00) |
CDKN2A | 65 (21%) | 241 |
0.022 (1.00) |
0.494 (1.00) |
0.0349 (1.00) |
0.583 (1.00) |
0.201 (1.00) |
0.206 (1.00) |
0.418 (1.00) |
0.113 (1.00) |
0.191 (1.00) |
0.15 (1.00) |
NFE2L2 | 17 (6%) | 289 |
0.807 (1.00) |
0.267 (1.00) |
0.125 (1.00) |
0.765 (1.00) |
1 (1.00) |
0.464 (1.00) |
0.248 (1.00) |
0.0736 (1.00) |
0.357 (1.00) |
0.471 (1.00) |
FAT1 | 72 (24%) | 234 |
0.24 (1.00) |
0.621 (1.00) |
0.794 (1.00) |
0.487 (1.00) |
0.152 (1.00) |
0.288 (1.00) |
0.885 (1.00) |
0.317 (1.00) |
0.162 (1.00) |
0.151 (1.00) |
JUB | 18 (6%) | 288 |
0.201 (1.00) |
0.181 (1.00) |
0.0646 (1.00) |
0.0816 (1.00) |
0.305 (1.00) |
0.221 (1.00) |
0.328 (1.00) |
1 (1.00) |
0.0121 (1.00) |
0.706 (1.00) |
MLL2 | 56 (18%) | 250 |
0.0727 (1.00) |
0.00657 (1.00) |
0.687 (1.00) |
0.521 (1.00) |
0.0532 (1.00) |
0.00795 (1.00) |
0.0529 (1.00) |
0.0102 (1.00) |
0.225 (1.00) |
0.0303 (1.00) |
FBXW7 | 15 (5%) | 291 |
0.76 (1.00) |
0.851 (1.00) |
0.092 (1.00) |
0.303 (1.00) |
0.881 (1.00) |
0.636 (1.00) |
0.945 (1.00) |
0.854 (1.00) |
0.872 (1.00) |
0.804 (1.00) |
ZNF750 | 13 (4%) | 293 |
0.396 (1.00) |
0.00628 (1.00) |
0.946 (1.00) |
0.353 (1.00) |
0.119 (1.00) |
0.128 (1.00) |
0.632 (1.00) |
1 (1.00) |
0.29 (1.00) |
0.692 (1.00) |
FLG | 48 (16%) | 258 |
0.733 (1.00) |
0.0404 (1.00) |
0.532 (1.00) |
0.575 (1.00) |
0.139 (1.00) |
0.223 (1.00) |
0.0631 (1.00) |
0.163 (1.00) |
0.0672 (1.00) |
0.275 (1.00) |
B2M | 7 (2%) | 299 |
0.241 (1.00) |
0.225 (1.00) |
0.515 (1.00) |
0.517 (1.00) |
0.141 (1.00) |
0.756 (1.00) |
0.157 (1.00) |
0.499 (1.00) |
||
IL32 | 4 (1%) | 302 |
0.0451 (1.00) |
0.129 (1.00) |
0.561 (1.00) |
1 (1.00) |
0.561 (1.00) |
0.669 (1.00) |
0.828 (1.00) |
1 (1.00) |
||
EP300 | 25 (8%) | 281 |
0.0376 (1.00) |
0.728 (1.00) |
0.769 (1.00) |
0.264 (1.00) |
0.00955 (1.00) |
0.00467 (1.00) |
0.352 (1.00) |
0.335 (1.00) |
0.232 (1.00) |
0.026 (1.00) |
RHOA | 4 (1%) | 302 |
0.724 (1.00) |
0.177 (1.00) |
0.379 (1.00) |
0.444 (1.00) |
0.245 (1.00) |
0.141 (1.00) |
0.246 (1.00) |
0.231 (1.00) |
0.139 (1.00) |
0.361 (1.00) |
HLA-A | 9 (3%) | 297 |
0.916 (1.00) |
0.711 (1.00) |
1 (1.00) |
1 (1.00) |
0.072 (1.00) |
0.0311 (1.00) |
0.634 (1.00) |
0.588 (1.00) |
0.175 (1.00) |
0.337 (1.00) |
CTCF | 11 (4%) | 295 |
0.248 (1.00) |
0.122 (1.00) |
0.393 (1.00) |
0.541 (1.00) |
0.636 (1.00) |
0.632 (1.00) |
0.861 (1.00) |
0.81 (1.00) |
0.66 (1.00) |
0.722 (1.00) |
RB1 | 10 (3%) | 296 |
0.0297 (1.00) |
0.00888 (1.00) |
0.282 (1.00) |
0.129 (1.00) |
0.00607 (1.00) |
0.00838 (1.00) |
0.0561 (1.00) |
1 (1.00) |
0.263 (1.00) |
0.0707 (1.00) |
TGFBR2 | 10 (3%) | 296 |
0.0814 (1.00) |
0.483 (1.00) |
0.469 (1.00) |
1 (1.00) |
0.313 (1.00) |
0.785 (1.00) |
0.919 (1.00) |
1 (1.00) |
0.159 (1.00) |
0.46 (1.00) |
NECAB1 | 6 (2%) | 300 |
0.0438 (1.00) |
1 (1.00) |
0.856 (1.00) |
0.672 (1.00) |
0.114 (1.00) |
0.0622 (1.00) |
0.773 (1.00) |
0.49 (1.00) |
0.769 (1.00) |
0.45 (1.00) |
KRTAP1-5 | 3 (1%) | 303 |
0.927 (1.00) |
1 (1.00) |
0.78 (1.00) |
0.63 (1.00) |
0.0245 (1.00) |
1 (1.00) |
0.37 (1.00) |
0.794 (1.00) |
||
MAPK1 | 4 (1%) | 302 |
0.808 (1.00) |
0.698 (1.00) |
0.569 (1.00) |
1 (1.00) |
0.691 (1.00) |
0.686 (1.00) |
0.69 (1.00) |
0.669 (1.00) |
0.685 (1.00) |
0.713 (1.00) |
PLSCR1 | 5 (2%) | 301 |
0.329 (1.00) |
0.291 (1.00) |
1 (1.00) |
1 (1.00) |
0.524 (1.00) |
0.526 (1.00) |
0.157 (1.00) |
0.442 (1.00) |
0.739 (1.00) |
0.761 (1.00) |
CNPY3 | 3 (1%) | 303 |
0.443 (1.00) |
0.66 (1.00) |
0.5 (1.00) |
0.499 (1.00) |
0.501 (1.00) |
0.59 (1.00) |
0.498 (1.00) |
0.794 (1.00) |
||
EPB41L3 | 16 (5%) | 290 |
0.815 (1.00) |
0.308 (1.00) |
0.253 (1.00) |
0.0152 (1.00) |
0.0509 (1.00) |
0.0132 (1.00) |
0.154 (1.00) |
0.202 (1.00) |
0.161 (1.00) |
0.185 (1.00) |
RAC1 | 9 (3%) | 297 |
0.302 (1.00) |
1 (1.00) |
1 (1.00) |
0.519 (1.00) |
0.195 (1.00) |
0.192 (1.00) |
0.218 (1.00) |
0.321 (1.00) |
0.496 (1.00) |
0.332 (1.00) |
CUL3 | 10 (3%) | 296 |
0.82 (1.00) |
0.336 (1.00) |
0.737 (1.00) |
0.636 (1.00) |
0.403 (1.00) |
0.852 (1.00) |
0.79 (1.00) |
0.359 (1.00) |
0.904 (1.00) |
0.567 (1.00) |
TRPV4 | 7 (2%) | 299 |
0.302 (1.00) |
0.412 (1.00) |
0.796 (1.00) |
0.27 (1.00) |
0.571 (1.00) |
0.0634 (1.00) |
0.569 (1.00) |
0.371 (1.00) |
0.714 (1.00) |
0.332 (1.00) |
PRB2 | 10 (3%) | 296 |
0.499 (1.00) |
0.0801 (1.00) |
0.888 (1.00) |
1 (1.00) |
0.669 (1.00) |
0.231 (1.00) |
0.667 (1.00) |
0.15 (1.00) |
0.235 (1.00) |
0.164 (1.00) |
PRB1 | 7 (2%) | 299 |
0.568 (1.00) |
0.639 (1.00) |
0.757 (1.00) |
0.672 (1.00) |
0.89 (1.00) |
0.639 (1.00) |
0.106 (1.00) |
1 (1.00) |
0.157 (1.00) |
0.797 (1.00) |
WHSC1 | 10 (3%) | 296 |
0.0792 (1.00) |
0.112 (1.00) |
0.284 (1.00) |
0.622 (1.00) |
0.855 (1.00) |
0.852 (1.00) |
0.174 (1.00) |
1 (1.00) |
0.0832 (1.00) |
0.93 (1.00) |
STEAP4 | 10 (3%) | 296 |
0.292 (1.00) |
0.0801 (1.00) |
0.175 (1.00) |
0.656 (1.00) |
0.0813 (1.00) |
0.0997 (1.00) |
0.0817 (1.00) |
1 (1.00) |
0.109 (1.00) |
0.137 (1.00) |
HIST1H1B | 7 (2%) | 299 |
0.0466 (1.00) |
0.152 (1.00) |
0.705 (1.00) |
0.822 (1.00) |
0.802 (1.00) |
0.717 (1.00) |
0.569 (1.00) |
0.108 (1.00) |
0.89 (1.00) |
0.131 (1.00) |
KCNA3 | 8 (3%) | 298 |
0.855 (1.00) |
0.105 (1.00) |
0.802 (1.00) |
0.0518 (1.00) |
0.606 (1.00) |
0.491 (1.00) |
0.907 (1.00) |
0.306 (1.00) |
0.582 (1.00) |
0.503 (1.00) |
EPDR1 | 6 (2%) | 300 |
0.45 (1.00) |
1 (1.00) |
0.561 (1.00) |
0.779 (1.00) |
0.327 (1.00) |
0.675 (1.00) |
0.88 (1.00) |
1 (1.00) |
1 (1.00) |
0.705 (1.00) |
SLC26A7 | 8 (3%) | 298 |
0.646 (1.00) |
0.606 (1.00) |
0.569 (1.00) |
0.209 (1.00) |
0.2 (1.00) |
0.311 (1.00) |
0.907 (1.00) |
0.764 (1.00) |
1 (1.00) |
0.828 (1.00) |
OR8D4 | 6 (2%) | 300 |
0.927 (1.00) |
0.618 (1.00) |
0.894 (1.00) |
0.438 (1.00) |
0.387 (1.00) |
1 (1.00) |
0.387 (1.00) |
0.72 (1.00) |
0.328 (1.00) |
0.264 (1.00) |
POU4F2 | 7 (2%) | 299 |
0.671 (1.00) |
0.802 (1.00) |
0.428 (1.00) |
0.404 (1.00) |
0.571 (1.00) |
0.563 (1.00) |
0.344 (1.00) |
0.756 (1.00) |
0.304 (1.00) |
0.332 (1.00) |
FCRL4 | 13 (4%) | 293 |
0.677 (1.00) |
0.406 (1.00) |
0.788 (1.00) |
1 (1.00) |
0.405 (1.00) |
0.106 (1.00) |
0.377 (1.00) |
0.833 (1.00) |
0.43 (1.00) |
0.572 (1.00) |
TXK | 3 (1%) | 303 |
0.417 (1.00) |
0.547 (1.00) |
0.78 (1.00) |
0.782 (1.00) |
0.114 (1.00) |
1 (1.00) |
P value = 1.27e-05 (Fisher's exact test), Q value = 0.0055
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 100 | 104 | 102 |
NSD1 MUTATED | 22 | 9 | 2 |
NSD1 WILD-TYPE | 78 | 95 | 100 |
P value = 0.000411 (Fisher's exact test), Q value = 0.17
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 117 | 93 | 89 |
NSD1 MUTATED | 23 | 3 | 7 |
NSD1 WILD-TYPE | 94 | 90 | 82 |
P value = 6.41e-06 (Fisher's exact test), Q value = 0.0028
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 97 | 84 | 118 |
NSD1 MUTATED | 3 | 4 | 26 |
NSD1 WILD-TYPE | 94 | 80 | 92 |
P value = 8.17e-05 (Chi-square test), Q value = 0.035
nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6 | CLUS_7 | CLUS_8 |
---|---|---|---|---|---|---|---|---|
ALL | 70 | 47 | 63 | 26 | 58 | 17 | 6 | 15 |
HRAS MUTATED | 0 | 0 | 9 | 0 | 1 | 0 | 0 | 0 |
HRAS WILD-TYPE | 70 | 47 | 54 | 26 | 57 | 17 | 6 | 15 |
P value = 1.7e-12 (Chi-square test), Q value = 7.4e-10
nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6 | CLUS_7 | CLUS_8 |
---|---|---|---|---|---|---|---|---|
ALL | 70 | 47 | 63 | 26 | 58 | 17 | 6 | 15 |
TP53 MUTATED | 59 | 36 | 20 | 14 | 47 | 16 | 6 | 14 |
TP53 WILD-TYPE | 11 | 11 | 43 | 12 | 11 | 1 | 0 | 1 |
P value = 0.000562 (Fisher's exact test), Q value = 0.24
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 100 | 104 | 102 |
NOTCH1 MUTATED | 18 | 9 | 30 |
NOTCH1 WILD-TYPE | 82 | 95 | 72 |
P value = 0.000428 (Fisher's exact test), Q value = 0.18
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 117 | 93 | 89 |
NOTCH1 MUTATED | 10 | 22 | 25 |
NOTCH1 WILD-TYPE | 107 | 71 | 64 |
P value = 2.54e-06 (Fisher's exact test), Q value = 0.0011
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 97 | 84 | 118 |
NOTCH1 MUTATED | 20 | 29 | 8 |
NOTCH1 WILD-TYPE | 77 | 55 | 110 |
P value = 0.000112 (Fisher's exact test), Q value = 0.048
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 89 | 119 | 96 |
NOTCH1 MUTATED | 26 | 9 | 21 |
NOTCH1 WILD-TYPE | 63 | 110 | 75 |
P value = 1.62e-05 (Chi-square test), Q value = 0.0069
nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6 | CLUS_7 | CLUS_8 |
---|---|---|---|---|---|---|---|---|
ALL | 70 | 47 | 63 | 26 | 58 | 17 | 6 | 15 |
CASP8 MUTATED | 1 | 0 | 16 | 3 | 4 | 1 | 1 | 0 |
CASP8 WILD-TYPE | 69 | 47 | 47 | 23 | 54 | 16 | 5 | 15 |
P value = 0.000335 (Fisher's exact test), Q value = 0.14
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 100 | 104 | 102 |
CASP8 MUTATED | 11 | 1 | 15 |
CASP8 WILD-TYPE | 89 | 103 | 87 |
P value = 3e-07 (Fisher's exact test), Q value = 0.00013
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 117 | 93 | 89 |
CASP8 MUTATED | 1 | 5 | 19 |
CASP8 WILD-TYPE | 116 | 88 | 70 |
P value = 5.28e-07 (Fisher's exact test), Q value = 0.00023
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 97 | 84 | 118 |
CASP8 MUTATED | 6 | 18 | 1 |
CASP8 WILD-TYPE | 91 | 66 | 117 |
P value = 0.000302 (Fisher's exact test), Q value = 0.13
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 74 | 106 | 88 |
CASP8 MUTATED | 14 | 2 | 8 |
CASP8 WILD-TYPE | 60 | 104 | 80 |
P value = 0.000357 (Fisher's exact test), Q value = 0.15
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 74 | 106 | 88 |
EPHA2 MUTATED | 8 | 0 | 2 |
EPHA2 WILD-TYPE | 66 | 106 | 86 |
P value = 1.35e-05 (Fisher's exact test), Q value = 0.0058
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 117 | 93 | 89 |
CSMD3 MUTATED | 43 | 9 | 18 |
CSMD3 WILD-TYPE | 74 | 84 | 71 |
P value = 6.66e-07 (Fisher's exact test), Q value = 0.00029
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 97 | 84 | 118 |
CSMD3 MUTATED | 9 | 15 | 46 |
CSMD3 WILD-TYPE | 88 | 69 | 72 |
P value = 0.000542 (Fisher's exact test), Q value = 0.23
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 89 | 119 | 96 |
CSMD3 MUTATED | 22 | 38 | 10 |
CSMD3 WILD-TYPE | 67 | 81 | 86 |
P value = 0.000137 (Fisher's exact test), Q value = 0.059
nPatients | CLUS_1 | CLUS_2 | CLUS_3 |
---|---|---|---|
ALL | 74 | 106 | 88 |
CSMD3 MUTATED | 16 | 34 | 7 |
CSMD3 WILD-TYPE | 58 | 72 | 81 |
-
Mutation data file = HNSC-TP.mutsig.cluster.txt
-
Molecular subtypes file = HNSC-TP.transferedmergedcluster.txt
-
Number of patients = 306
-
Number of significantly mutated genes = 45
-
Number of Molecular subtypes = 10
-
Exclude genes that fewer than K tumors have mutations, K = 3
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
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
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.
This is an experimental feature. The full results of the analysis summarized in this report can be downloaded from the TCGA Data Coordination Center.