Correlation between gene mutation status and molecular subtypes

Lung Squamous Cell Carcinoma (Primary solid tumor)

23 September 2013 | analyses__2013_09_23

Maintainer Information

Citation Information

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Correlation between gene mutation status and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1XK8CX0

Overview

Introduction

This pipeline computes the correlation between significantly recurrent gene mutations and molecular subtypes.

Summary

Testing the association between mutation status of 16 genes and 12 molecular subtypes across 178 patients, 10 significant findings detected with P value < 0.05 and Q value < 0.25.

CDKN2A mutation correlated to 'MRNA_CNMF'.
TP53 mutation correlated to 'CN_CNMF', 'METHLYATION_CNMF', and 'MRNASEQ_CNMF'.
NFE2L2 mutation correlated to 'MRNA_CNMF', 'MRNA_CHIERARCHICAL', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', and 'MIRSEQ_CHIERARCHICAL'.
KEAP1 mutation correlated to 'MRNA_CHIERARCHICAL'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 16 genes and 12 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 10 significant findings detected.


		Clinical Features	MRNA CNMF	MRNA CHIERARCHICAL	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	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	Fisher's exact test	Fisher's exact test	Fisher's exact test
NFE2L2	27 (15%)	151	0.00024 (0.0415)	0.00073 (0.126)	0.0194 (1.00)	0.0365 (1.00)	0.253 (1.00)	0.144 (1.00)	3.23e-06 (0.000569)	1.36e-06 (0.000243)	0.0289 (1.00)	1.75e-06 (0.000309)	0.589 (1.00)	0.14 (1.00)
TP53	141 (79%)	37	0.0449 (1.00)	0.038 (1.00)	4.15e-05 (0.00726)	0.0014 (0.238)	1 (1.00)	0.902 (1.00)	0.000841 (0.144)	0.0131 (1.00)	0.136 (1.00)	0.519 (1.00)	0.824 (1.00)	0.726 (1.00)
CDKN2A	26 (15%)	152	0.00141 (0.239)	0.0482 (1.00)	0.0119 (1.00)	0.668 (1.00)	0.34 (1.00)	0.204 (1.00)	0.353 (1.00)	0.667 (1.00)	0.783 (1.00)	1 (1.00)	1 (1.00)	0.0993 (1.00)
KEAP1	22 (12%)	156	0.0015 (0.251)	0.000229 (0.0398)	0.122 (1.00)	0.0758 (1.00)	0.204 (1.00)	0.0963 (1.00)	0.159 (1.00)	0.0438 (1.00)	0.699 (1.00)	0.823 (1.00)	0.00504 (0.842)	0.61 (1.00)
PIK3CA	27 (15%)	151	0.69 (1.00)	0.597 (1.00)	0.258 (1.00)	0.545 (1.00)	1 (1.00)	0.709 (1.00)	0.365 (1.00)	0.891 (1.00)	0.614 (1.00)	0.739 (1.00)	0.456 (1.00)	0.726 (1.00)
PTEN	14 (8%)	164	0.381 (1.00)	0.448 (1.00)	0.226 (1.00)	0.134 (1.00)	0.721 (1.00)	0.473 (1.00)	0.636 (1.00)	0.146 (1.00)	0.574 (1.00)	0.43 (1.00)	0.357 (1.00)	1 (1.00)
CSMD3	81 (46%)	97	0.323 (1.00)	0.931 (1.00)	0.738 (1.00)	0.508 (1.00)	0.265 (1.00)	0.769 (1.00)	0.529 (1.00)	0.816 (1.00)	0.664 (1.00)	1 (1.00)	0.419 (1.00)	0.164 (1.00)
MLL2	36 (20%)	142	0.301 (1.00)	0.926 (1.00)	0.485 (1.00)	0.314 (1.00)	0.696 (1.00)	0.22 (1.00)	0.442 (1.00)	0.625 (1.00)	0.986 (1.00)	0.6 (1.00)	0.614 (1.00)	1 (1.00)
FBXW7	11 (6%)	167	0.493 (1.00)	0.946 (1.00)	0.925 (1.00)		0.621 (1.00)	0.785 (1.00)	0.899 (1.00)	0.718 (1.00)	1 (1.00)	0.797 (1.00)		0.49 (1.00)
RB1	12 (7%)	166	0.314 (1.00)	0.189 (1.00)	0.807 (1.00)	0.108 (1.00)	0.657 (1.00)	0.433 (1.00)	1 (1.00)	0.354 (1.00)	0.574 (1.00)	0.911 (1.00)		1 (1.00)
HS6ST1	5 (3%)	173	0.276 (1.00)	0.294 (1.00)	0.538 (1.00)				0.572 (1.00)	0.078 (1.00)	1 (1.00)	1 (1.00)
ZNF567	3 (2%)	175			0.358 (1.00)		0.359 (1.00)	0.424 (1.00)	0.45 (1.00)	0.427 (1.00)	0.25 (1.00)	0.188 (1.00)		1 (1.00)
ELTD1	18 (10%)	160	0.0382 (1.00)	0.324 (1.00)	0.0744 (1.00)	0.6 (1.00)	0.341 (1.00)	0.648 (1.00)	0.578 (1.00)	0.434 (1.00)	0.0916 (1.00)	0.721 (1.00)	0.305 (1.00)	0.419 (1.00)
ASCL4	6 (3%)	172	0.0969 (1.00)	0.534 (1.00)	1 (1.00)	0.783 (1.00)	0.817 (1.00)	0.835 (1.00)	0.318 (1.00)	0.245 (1.00)	0.909 (1.00)	0.216 (1.00)
OR2G6	16 (9%)	162	0.381 (1.00)	0.23 (1.00)	0.847 (1.00)	1 (1.00)	1 (1.00)	0.717 (1.00)	0.185 (1.00)	0.0446 (1.00)	0.406 (1.00)	0.244 (1.00)	0.668 (1.00)	0.61 (1.00)
NOTCH1	14 (8%)	164	0.817 (1.00)	0.92 (1.00)	0.463 (1.00)	0.0342 (1.00)	0.591 (1.00)	0.824 (1.00)	0.678 (1.00)	0.407 (1.00)	0.183 (1.00)	0.843 (1.00)	0.483 (1.00)	0.668 (1.00)

'CDKN2A MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.00141 (Fisher's exact test), Q value = 0.24

Table S1. Gene #1: 'CDKN2A MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	37	48	17	19
CDKN2A MUTATED	0	13	3	2
CDKN2A WILD-TYPE	37	35	14	17

Figure S1. Get High-res Image Gene #1: 'CDKN2A MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

'TP53 MUTATION STATUS' versus 'CN_CNMF'

P value = 4.15e-05 (Fisher's exact test), Q value = 0.0073

Table S2. Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #3: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	64	69	45
TP53 MUTATED	39	63	39
TP53 WILD-TYPE	25	6	6

Figure S2. Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #3: 'CN_CNMF'

'TP53 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.0014 (Fisher's exact test), Q value = 0.24

Table S3. Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #4: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	27	29	18
TP53 MUTATED	16	28	15
TP53 WILD-TYPE	11	1	3

Figure S3. Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #4: 'METHLYATION_CNMF'

'TP53 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.000841 (Fisher's exact test), Q value = 0.14

Table S4. Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #7: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	42	61	49	26
TP53 MUTATED	33	55	40	13
TP53 WILD-TYPE	9	6	9	13

Figure S4. Get High-res Image Gene #2: 'TP53 MUTATION STATUS' versus Clinical Feature #7: 'MRNASEQ_CNMF'

'NFE2L2 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.00024 (Fisher's exact test), Q value = 0.041

Table S5. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	37	48	17	19
NFE2L2 MUTATED	0	14	1	1
NFE2L2 WILD-TYPE	37	34	16	18

Figure S5. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

'NFE2L2 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.00073 (Fisher's exact test), Q value = 0.13

Table S6. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	7	52	20	42
NFE2L2 MUTATED	1	14	0	1
NFE2L2 WILD-TYPE	6	38	20	41

Figure S6. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

'NFE2L2 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 3.23e-06 (Fisher's exact test), Q value = 0.00057

Table S7. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #7: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	42	61	49	26
NFE2L2 MUTATED	2	21	1	3
NFE2L2 WILD-TYPE	40	40	48	23

Figure S7. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #7: 'MRNASEQ_CNMF'

'NFE2L2 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1.36e-06 (Fisher's exact test), Q value = 0.00024

Table S8. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #8: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	34	60	84
NFE2L2 MUTATED	1	21	5
NFE2L2 WILD-TYPE	33	39	79

Figure S8. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #8: 'MRNASEQ_CHIERARCHICAL'

'NFE2L2 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 1.75e-06 (Fisher's exact test), Q value = 0.00031

Table S9. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #10: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	30	32	100
NFE2L2 MUTATED	14	0	12
NFE2L2 WILD-TYPE	16	32	88

Figure S9. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #10: 'MIRSEQ_CHIERARCHICAL'

'KEAP1 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.000229 (Fisher's exact test), Q value = 0.04

Table S10. Gene #6: 'KEAP1 MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	7	52	20	42
KEAP1 MUTATED	3	13	0	1
KEAP1 WILD-TYPE	4	39	20	41

Figure S10. Get High-res Image Gene #6: 'KEAP1 MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

Methods & Data

Input

Mutation data file = LUSC-TP.mutsig.cluster.txt
Molecular subtypes file = LUSC-TP.transferedmergedcluster.txt
Number of patients = 178
Number of significantly mutated genes = 16
Number of Molecular subtypes = 12
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

In addition to the links below, the full results of the analysis summarized in this report can also be downloaded programmatically using firehose_get, or interactively from either the Broad GDAC website or TCGA Data Coordination Center Portal.

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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