Thyroid Adenocarcinoma: Correlation between gene mutation status and molecular subtypes<BR>(primary solid tumor cohort)

Thyroid Adenocarcinoma: Correlation between gene mutation status and molecular subtypes
(primary solid 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 molecular subtypes.

Summary

Testing the association between mutation status of 41 genes and 8 molecular subtypes across 323 patients, 20 significant findings detected with P value < 0.05 and Q value < 0.25.

BRAF mutation correlated to 'METHLYATION_CNMF', 'RPPA_CNMF', 'RPPA_CHIERARCHICAL', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', 'MIRSEQ_CNMF', and 'MIRSEQ_CHIERARCHICAL'.
HRAS mutation correlated to 'CN_CNMF', 'METHLYATION_CNMF', 'RPPA_CNMF', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', 'MIRSEQ_CNMF', and 'MIRSEQ_CHIERARCHICAL'.
NRAS mutation correlated to 'METHLYATION_CNMF', 'RPPA_CHIERARCHICAL', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', 'MIRSEQ_CNMF', and 'MIRSEQ_CHIERARCHICAL'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 41 genes and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 20 significant findings detected.


		Clinical Features	CN CNMF	METHLYATION CNMF	RPPA CNMF	RPPA CHIERARCHICAL	MRNASEQ CNMF	MRNASEQ CHIERARCHICAL	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL
	nMutated (%)	nWild-Type	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
BRAF	183 (57%)	140	0.0194 (1.00)	3.62e-38 (9.99e-36)	9.4e-07 (0.000252)	2.51e-11 (6.84e-09)	4.03e-46 (1.13e-43)	1.56e-39 (4.31e-37)	9.88e-42 (2.75e-39)	1.03e-43 (2.86e-41)
HRAS	12 (4%)	311	0.000222 (0.0582)	1.48e-06 (0.000393)	9.23e-05 (0.0243)	0.00529 (1.00)	1.37e-05 (0.00362)	6.79e-06 (0.0018)	1.31e-06 (0.00035)	3.85e-07 (0.000104)
NRAS	26 (8%)	297	0.00692 (1.00)	6.06e-14 (1.67e-11)	1 (1.00)	0.000583 (0.152)	4.7e-11 (1.27e-08)	4.03e-11 (1.09e-08)	9.19e-13 (2.51e-10)	2.47e-13 (6.78e-11)
EMG1	6 (2%)	317	0.548 (1.00)	1 (1.00)	0.327 (1.00)	0.0846 (1.00)	1 (1.00)	1 (1.00)	1 (1.00)	0.778 (1.00)
PTTG1IP	4 (1%)	319	1 (1.00)	1 (1.00)			0.242 (1.00)	0.252 (1.00)	0.469 (1.00)	0.393 (1.00)
RPTN	8 (2%)	315	0.805 (1.00)	0.442 (1.00)	0.265 (1.00)	0.801 (1.00)	0.0249 (1.00)	0.415 (1.00)	0.82 (1.00)	0.666 (1.00)
EIF1AX	5 (2%)	318	0.731 (1.00)	0.0278 (1.00)	0.444 (1.00)	0.132 (1.00)	0.0621 (1.00)	0.0109 (1.00)	0.0581 (1.00)	0.236 (1.00)
CCDC15	5 (2%)	318	0.731 (1.00)	0.115 (1.00)	1 (1.00)	0.381 (1.00)	0.132 (1.00)	0.136 (1.00)	0.63 (1.00)	0.53 (1.00)
ZNF845	6 (2%)	317	0.42 (1.00)	0.637 (1.00)	0.639 (1.00)	0.125 (1.00)	0.943 (1.00)	0.166 (1.00)	0.777 (1.00)	0.328 (1.00)
ZNF878	4 (1%)	319	1 (1.00)	0.487 (1.00)			0.0454 (1.00)	0.833 (1.00)	0.691 (1.00)	1 (1.00)
TG	16 (5%)	307	1 (1.00)	0.0205 (1.00)	0.34 (1.00)	0.492 (1.00)	0.406 (1.00)	0.293 (1.00)	0.0452 (1.00)	0.0253 (1.00)
PRB2	6 (2%)	317	1 (1.00)	0.637 (1.00)	0.0801 (1.00)	0.851 (1.00)	0.474 (1.00)	0.723 (1.00)	0.522 (1.00)	0.598 (1.00)
R3HDM2	4 (1%)	319	0.0124 (1.00)	0.063 (1.00)			0.0699 (1.00)	0.0388 (1.00)	0.0191 (1.00)	0.00822 (1.00)
IL32	3 (1%)	320	1 (1.00)	0.742 (1.00)			1 (1.00)	0.78 (1.00)	0.202 (1.00)	0.645 (1.00)
TMCO2	3 (1%)	320	1 (1.00)	0.416 (1.00)	0.778 (1.00)	0.2 (1.00)	0.492 (1.00)	0.303 (1.00)	0.401 (1.00)	0.778 (1.00)
PPTC7	3 (1%)	320	0.0791 (1.00)	0.0627 (1.00)			0.172 (1.00)	0.0916 (1.00)	0.299 (1.00)	0.403 (1.00)
MUC7	5 (2%)	318	0.731 (1.00)	0.372 (1.00)	0.683 (1.00)	0.26 (1.00)	0.805 (1.00)	0.848 (1.00)	0.866 (1.00)	0.629 (1.00)
LYPD3	3 (1%)	320	0.547 (1.00)	0.416 (1.00)			0.492 (1.00)	0.303 (1.00)	0.644 (1.00)	0.778 (1.00)
TMEM90B	3 (1%)	320	0.135 (1.00)	1 (1.00)			1 (1.00)	0.78 (1.00)	1 (1.00)	1 (1.00)
ZNF799	5 (2%)	318	0.465 (1.00)	1 (1.00)	0.505 (1.00)	1 (1.00)	0.592 (1.00)	0.848 (1.00)	0.451 (1.00)	1 (1.00)
PPM1D	5 (2%)	318	1 (1.00)	1 (1.00)	0.778 (1.00)	0.125 (1.00)	0.693 (1.00)	0.848 (1.00)	0.866 (1.00)	0.329 (1.00)
MAP3K3	4 (1%)	319	0.061 (1.00)	0.224 (1.00)	0.459 (1.00)	0.0846 (1.00)	0.274 (1.00)	0.184 (1.00)	0.469 (1.00)	0.555 (1.00)
TROAP	3 (1%)	320	1 (1.00)	0.742 (1.00)	0.778 (1.00)	0.535 (1.00)	0.746 (1.00)	1 (1.00)	0.519 (1.00)	0.403 (1.00)
SYNPO2L	3 (1%)	320	0.547 (1.00)	1 (1.00)			1 (1.00)	0.78 (1.00)	1 (1.00)	1 (1.00)
ATAD2	4 (1%)	319	1 (1.00)	0.823 (1.00)			0.808 (1.00)	1 (1.00)	0.691 (1.00)	1 (1.00)
KRAS	3 (1%)	320	1 (1.00)	0.0627 (1.00)			0.172 (1.00)	0.0916 (1.00)	0.0616 (1.00)	0.0276 (1.00)
SLC5A11	3 (1%)	320	0.547 (1.00)	0.742 (1.00)					0.299 (1.00)	0.403 (1.00)
PRG4	4 (1%)	319	0.23 (1.00)	0.104 (1.00)			0.0128 (1.00)	0.142 (1.00)	0.469 (1.00)	0.555 (1.00)
SCUBE2	3 (1%)	320	1 (1.00)	0.281 (1.00)			0.314 (1.00)	0.303 (1.00)	0.644 (1.00)	0.522 (1.00)
ZNF479	3 (1%)	320	1 (1.00)	0.742 (1.00)			1 (1.00)	0.78 (1.00)	0.519 (1.00)	1 (1.00)
SREBF2	3 (1%)	320	1 (1.00)	0.742 (1.00)			0.568 (1.00)	1 (1.00)	0.401 (1.00)	0.778 (1.00)
SLC26A11	3 (1%)	320	0.0791 (1.00)	1 (1.00)			0.368 (1.00)	0.78 (1.00)	0.778 (1.00)	0.301 (1.00)
TSC22D1	3 (1%)	320	1 (1.00)	1 (1.00)			0.746 (1.00)	1 (1.00)	0.778 (1.00)	0.645 (1.00)
ANKRD30A	5 (2%)	318	0.731 (1.00)	0.462 (1.00)			0.749 (1.00)	0.507 (1.00)	0.74 (1.00)	0.865 (1.00)
FAM155A	4 (1%)	319	0.144 (1.00)	0.156 (1.00)	0.778 (1.00)	0.535 (1.00)			0.0372 (1.00)	0.555 (1.00)
SLA	3 (1%)	320	0.547 (1.00)	0.0627 (1.00)	0.286 (1.00)	0.285 (1.00)	0.172 (1.00)	0.0916 (1.00)	0.0616 (1.00)	0.0276 (1.00)
ZFHX3	10 (3%)	313	0.171 (1.00)	0.616 (1.00)	0.48 (1.00)	0.632 (1.00)	0.794 (1.00)	0.437 (1.00)	0.613 (1.00)	0.723 (1.00)
ARMCX3	3 (1%)	320	0.547 (1.00)	0.742 (1.00)			0.646 (1.00)	0.213 (1.00)	0.519 (1.00)	0.202 (1.00)
SLC25A45	3 (1%)	320	0.135 (1.00)	1 (1.00)					0.202 (1.00)	0.403 (1.00)
COL5A3	6 (2%)	317	0.752 (1.00)	0.317 (1.00)	0.778 (1.00)	0.758 (1.00)	0.044 (1.00)	0.753 (1.00)	0.877 (1.00)	0.523 (1.00)
CDC27	3 (1%)	320	1 (1.00)	1 (1.00)			0.368 (1.00)	0.0446 (1.00)	0.778 (1.00)	0.301 (1.00)

'BRAF MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 3.62e-38 (Fisher's exact test), Q value = 1e-35

Table S1. Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	105	52	166
BRAF MUTATED	10	30	143
BRAF WILD-TYPE	95	22	23

Figure S1. Get High-res Image Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #2: 'METHLYATION_CNMF'

'BRAF MUTATION STATUS' versus 'RPPA_CNMF'

P value = 9.4e-07 (Fisher's exact test), Q value = 0.00025

Table S2. Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #3: 'RPPA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	62	76	79
BRAF MUTATED	19	57	42
BRAF WILD-TYPE	43	19	37

Figure S2. Get High-res Image Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #3: 'RPPA_CNMF'

'BRAF MUTATION STATUS' versus 'RPPA_CHIERARCHICAL'

P value = 2.51e-11 (Fisher's exact test), Q value = 6.8e-09

Table S3. Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #4: 'RPPA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	96	32	89
BRAF MUTATED	30	16	72
BRAF WILD-TYPE	66	16	17

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

'BRAF MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 4.03e-46 (Fisher's exact test), Q value = 1.1e-43

Table S4. Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #5: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	102	36	70	95
BRAF MUTATED	6	20	57	90
BRAF WILD-TYPE	96	16	13	5

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

'BRAF MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1.56e-39 (Fisher's exact test), Q value = 4.3e-37

Table S5. Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #6: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	110	136	57
BRAF MUTATED	11	120	42
BRAF WILD-TYPE	99	16	15

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

'BRAF MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 9.88e-42 (Fisher's exact test), Q value = 2.7e-39

Table S6. Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #7: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	105	119	98
BRAF MUTATED	6	103	73
BRAF WILD-TYPE	99	16	25

Figure S6. Get High-res Image Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #7: 'MIRSEQ_CNMF'

'BRAF MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 1.03e-43 (Fisher's exact test), Q value = 2.9e-41

Table S7. Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #8: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	118	106	98
BRAF MUTATED	94	86	2
BRAF WILD-TYPE	24	20	96

Figure S7. Get High-res Image Gene #1: 'BRAF MUTATION STATUS' versus Clinical Feature #8: 'MIRSEQ_CHIERARCHICAL'

'HRAS MUTATION STATUS' versus 'CN_CNMF'

P value = 0.000222 (Fisher's exact test), Q value = 0.058

Table S8. Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	25	246	49
HRAS MUTATED	0	4	8
HRAS WILD-TYPE	25	242	41

Figure S8. Get High-res Image Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #1: 'CN_CNMF'

'HRAS MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 1.48e-06 (Fisher's exact test), Q value = 0.00039

Table S9. Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	105	52	166
HRAS MUTATED	12	0	0
HRAS WILD-TYPE	93	52	166

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

'HRAS MUTATION STATUS' versus 'RPPA_CNMF'

P value = 9.23e-05 (Fisher's exact test), Q value = 0.024

Table S10. Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #3: 'RPPA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	62	76	79
HRAS MUTATED	9	2	0
HRAS WILD-TYPE	53	74	79

Figure S10. Get High-res Image Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #3: 'RPPA_CNMF'

'HRAS MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 1.37e-05 (Fisher's exact test), Q value = 0.0036

Table S11. Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #5: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	102	36	70	95
HRAS MUTATED	12	0	0	0
HRAS WILD-TYPE	90	36	70	95

Figure S11. Get High-res Image Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #5: 'MRNASEQ_CNMF'

'HRAS MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 6.79e-06 (Fisher's exact test), Q value = 0.0018

Table S12. Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #6: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	110	136	57
HRAS MUTATED	12	0	0
HRAS WILD-TYPE	98	136	57

Figure S12. Get High-res Image Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #6: 'MRNASEQ_CHIERARCHICAL'

'HRAS MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 1.31e-06 (Fisher's exact test), Q value = 0.00035

Table S13. Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #7: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	105	119	98
HRAS MUTATED	12	0	0
HRAS WILD-TYPE	93	119	98

Figure S13. Get High-res Image Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #7: 'MIRSEQ_CNMF'

'HRAS MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 3.85e-07 (Fisher's exact test), Q value = 1e-04

Table S14. Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #8: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	118	106	98
HRAS MUTATED	0	0	12
HRAS WILD-TYPE	118	106	86

Figure S14. Get High-res Image Gene #3: 'HRAS MUTATION STATUS' versus Clinical Feature #8: 'MIRSEQ_CHIERARCHICAL'

'NRAS MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 6.06e-14 (Fisher's exact test), Q value = 1.7e-11

Table S15. Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	105	52	166
NRAS MUTATED	26	0	0
NRAS WILD-TYPE	79	52	166

Figure S15. Get High-res Image Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #2: 'METHLYATION_CNMF'

'NRAS MUTATION STATUS' versus 'RPPA_CHIERARCHICAL'

P value = 0.000583 (Fisher's exact test), Q value = 0.15

Table S16. Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #4: 'RPPA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	96	32	89
NRAS MUTATED	9	5	0
NRAS WILD-TYPE	87	27	89

Figure S16. Get High-res Image Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #4: 'RPPA_CHIERARCHICAL'

'NRAS MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 4.7e-11 (Fisher's exact test), Q value = 1.3e-08

Table S17. Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #5: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	102	36	70	95
NRAS MUTATED	23	0	0	0
NRAS WILD-TYPE	79	36	70	95

Figure S17. Get High-res Image Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #5: 'MRNASEQ_CNMF'

'NRAS MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 4.03e-11 (Fisher's exact test), Q value = 1.1e-08

Table S18. Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #6: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	110	136	57
NRAS MUTATED	23	0	0
NRAS WILD-TYPE	87	136	57

Figure S18. Get High-res Image Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #6: 'MRNASEQ_CHIERARCHICAL'

'NRAS MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 9.19e-13 (Fisher's exact test), Q value = 2.5e-10

Table S19. Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #7: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	105	119	98
NRAS MUTATED	25	0	1
NRAS WILD-TYPE	80	119	97

Figure S19. Get High-res Image Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #7: 'MIRSEQ_CNMF'

'NRAS MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 2.47e-13 (Fisher's exact test), Q value = 6.8e-11

Table S20. Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #8: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	118	106	98
NRAS MUTATED	1	0	25
NRAS WILD-TYPE	117	106	73

Figure S20. Get High-res Image Gene #4: 'NRAS MUTATION STATUS' versus Clinical Feature #8: 'MIRSEQ_CHIERARCHICAL'

Methods & Data

Input

Mutation data file = THCA-TP.mutsig.cluster.txt
Molecular subtypes file = THCA-TP.transferedmergedcluster.txt
Number of patients = 323
Number of significantly mutated genes = 41
Number of Molecular subtypes = 8
Exclude genes that fewer than K tumors have mutations, K = 3

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] 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)

[2] 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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