Correlation between gene mutation status and molecular subtypes

Lung Squamous Cell Carcinoma (Primary solid tumor)

23 May 2013 | analyses__2013_05_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/C16M34WK

Overview

Introduction

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

Summary

Testing the association between mutation status of 17 genes and 12 molecular subtypes across 177 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'.
NFE2L2 mutation correlated to 'MRNA_CNMF', 'MRNA_CHIERARCHICAL', 'CN_CNMF', 'MRNASEQ_CNMF', 'MRNASEQ_CHIERARCHICAL', 'MIRSEQ_CNMF', 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 17 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%)	150	0.000287 (0.0526)	0.000811 (0.146)	0.00137 (0.246)	0.0471 (1.00)	0.253 (1.00)	0.144 (1.00)	9.84e-07 (0.000184)	1.16e-05 (0.00216)	0.000528 (0.0961)	3.54e-05 (0.00654)	0.0996 (1.00)	0.00249 (0.436)
CDKN2A	26 (15%)	151	0.00138 (0.246)	0.053 (1.00)	0.00469 (0.816)	0.604 (1.00)	0.34 (1.00)	0.204 (1.00)	0.423 (1.00)	0.208 (1.00)	0.899 (1.00)	0.531 (1.00)	1 (1.00)	1 (1.00)
TP53	141 (80%)	36	0.0825 (1.00)	0.0522 (1.00)	0.000696 (0.126)	0.00222 (0.391)	1 (1.00)	0.902 (1.00)	0.0204 (1.00)	0.0243 (1.00)	0.565 (1.00)	0.525 (1.00)	0.0113 (1.00)	0.331 (1.00)
KEAP1	22 (12%)	155	0.00163 (0.288)	0.000253 (0.0465)	0.0644 (1.00)	0.0712 (1.00)	0.204 (1.00)	0.0963 (1.00)	0.12 (1.00)	0.00961 (1.00)	0.875 (1.00)	0.126 (1.00)	0.414 (1.00)	0.367 (1.00)
PIK3CA	27 (15%)	150	0.645 (1.00)	0.586 (1.00)	0.457 (1.00)	1 (1.00)	1 (1.00)	0.709 (1.00)	0.289 (1.00)	0.924 (1.00)	0.38 (1.00)	0.58 (1.00)	0.817 (1.00)	0.502 (1.00)
PTEN	14 (8%)	163	0.376 (1.00)	0.427 (1.00)	0.321 (1.00)	0.151 (1.00)	0.721 (1.00)	0.473 (1.00)	0.556 (1.00)	0.152 (1.00)	0.201 (1.00)	0.659 (1.00)	0.406 (1.00)	0.836 (1.00)
CSMD3	81 (46%)	96	0.238 (1.00)	0.887 (1.00)	0.945 (1.00)	0.303 (1.00)	0.265 (1.00)	0.769 (1.00)	0.667 (1.00)	0.519 (1.00)	0.946 (1.00)	0.808 (1.00)	0.766 (1.00)	0.934 (1.00)
MLL2	35 (20%)	142	0.144 (1.00)	0.833 (1.00)	0.471 (1.00)	0.398 (1.00)	0.696 (1.00)	0.22 (1.00)	0.511 (1.00)	0.519 (1.00)	0.726 (1.00)	0.758 (1.00)	0.466 (1.00)	0.41 (1.00)
FBXW7	11 (6%)	166	0.458 (1.00)	1 (1.00)	0.736 (1.00)		0.621 (1.00)	0.785 (1.00)	0.945 (1.00)	0.706 (1.00)	0.888 (1.00)	1 (1.00)
RB1	12 (7%)	165	0.343 (1.00)	0.198 (1.00)	0.489 (1.00)	0.838 (1.00)	0.657 (1.00)	0.433 (1.00)	0.623 (1.00)	0.297 (1.00)	0.905 (1.00)	0.719 (1.00)
HS6ST1	5 (3%)	172	0.269 (1.00)	0.295 (1.00)	0.623 (1.00)				0.542 (1.00)	0.0677 (1.00)	1 (1.00)	1 (1.00)
ZNF567	3 (2%)	174			0.308 (1.00)		0.359 (1.00)	0.424 (1.00)	0.378 (1.00)	0.0748 (1.00)	0.498 (1.00)	0.259 (1.00)
ELTD1	18 (10%)	159	0.0294 (1.00)	0.307 (1.00)	0.198 (1.00)	0.597 (1.00)	0.341 (1.00)	0.648 (1.00)	0.252 (1.00)	0.341 (1.00)	0.19 (1.00)	0.809 (1.00)	0.762 (1.00)	0.289 (1.00)
ASCL4	6 (3%)	171	0.0924 (1.00)	0.534 (1.00)	0.603 (1.00)	0.787 (1.00)	0.817 (1.00)	0.835 (1.00)	0.722 (1.00)	0.183 (1.00)	0.496 (1.00)	0.734 (1.00)
OR2G6	16 (9%)	161	0.366 (1.00)	0.211 (1.00)	0.128 (1.00)	1 (1.00)	1 (1.00)	0.717 (1.00)	0.306 (1.00)	0.278 (1.00)	0.509 (1.00)	0.448 (1.00)	1 (1.00)	0.367 (1.00)
HLA-A	6 (3%)	171	0.0391 (1.00)	0.33 (1.00)	0.373 (1.00)	0.176 (1.00)	1 (1.00)	0.513 (1.00)	0.123 (1.00)	0.122 (1.00)	0.705 (1.00)	0.625 (1.00)	0.299 (1.00)	0.118 (1.00)
NOTCH1	14 (8%)	163	0.812 (1.00)	0.921 (1.00)	0.734 (1.00)	0.0466 (1.00)	0.591 (1.00)	0.824 (1.00)	0.812 (1.00)	0.568 (1.00)	0.224 (1.00)	0.169 (1.00)	0.742 (1.00)	0.515 (1.00)

'CDKN2A MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.00138 (Fisher's exact test), Q value = 0.25

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	16	19
CDKN2A MUTATED	0	13	3	2
CDKN2A WILD-TYPE	37	35	13	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 = 0.000696 (Fisher's exact test), Q value = 0.13

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

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	55	60	62
TP53 MUTATED	34	53	54
TP53 WILD-TYPE	21	7	8

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

'NFE2L2 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.000287 (Fisher's exact test), Q value = 0.053

Table S3. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	37	48	16	19
NFE2L2 MUTATED	0	14	1	1
NFE2L2 WILD-TYPE	37	34	15	18

Figure S3. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

'NFE2L2 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.000811 (Fisher's exact test), Q value = 0.15

Table S4. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	7	52	20	41
NFE2L2 MUTATED	1	14	0	1
NFE2L2 WILD-TYPE	6	38	20	40

Figure S4. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

'NFE2L2 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.00137 (Fisher's exact test), Q value = 0.25

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

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	55	60	62
NFE2L2 MUTATED	7	17	3
NFE2L2 WILD-TYPE	48	43	59

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

'NFE2L2 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 9.84e-07 (Fisher's exact test), Q value = 0.00018

Table S6. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #7: 'MRNASEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	35	62	53	27
NFE2L2 MUTATED	2	22	1	2
NFE2L2 WILD-TYPE	33	40	52	25

Figure S6. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #7: 'MRNASEQ_CNMF'

'NFE2L2 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1.16e-05 (Fisher's exact test), Q value = 0.0022

Table S7. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #8: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	64	30	83
NFE2L2 MUTATED	21	1	5
NFE2L2 WILD-TYPE	43	29	78

Figure S7. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #8: 'MRNASEQ_CHIERARCHICAL'

'NFE2L2 MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.000528 (Fisher's exact test), Q value = 0.096

Table S8. Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #9: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	104	27	30
NFE2L2 MUTATED	13	1	12
NFE2L2 WILD-TYPE	91	26	18

Figure S8. Get High-res Image Gene #3: 'NFE2L2 MUTATION STATUS' versus Clinical Feature #9: 'MIRSEQ_CNMF'

'NFE2L2 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 3.54e-05 (Fisher's exact test), Q value = 0.0065

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

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	39	88	34
NFE2L2 MUTATED	1	11	14
NFE2L2 WILD-TYPE	38	77	20

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 = 0.000253 (Fisher's exact test), Q value = 0.046

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	41
KEAP1 MUTATED	3	13	0	1
KEAP1 WILD-TYPE	4	39	20	40

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 = 177
Number of significantly mutated genes = 17
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

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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