Correlation between gene mutation status and molecular subtypes

Colon Adenocarcinoma (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/C1M32T28

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 7 molecular subtypes across 154 patients, 7 significant findings detected with P value < 0.05 and Q value < 0.25.

BRAF mutation correlated to 'MRNA_CNMF', 'MRNA_CHIERARCHICAL', and 'CN_CNMF'.
KRAS mutation correlated to 'MRNA_CHIERARCHICAL'.
TP53 mutation correlated to 'MRNA_CNMF' and 'CN_CNMF'.
FBXW7 mutation correlated to 'CN_CNMF'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 16 genes and 7 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 7 significant findings detected.


		Clinical Features	MRNA CNMF	MRNA CHIERARCHICAL	CN CNMF	RPPA CNMF	RPPA 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
BRAF	20 (13%)	134	3.29e-07 (3.36e-05)	4.37e-08 (4.5e-06)	9.33e-05 (0.00943)	0.722 (1.00)	0.926 (1.00)	0.462 (1.00)	1 (1.00)
TP53	74 (48%)	80	0.00226 (0.222)	0.013 (1.00)	9.19e-10 (9.56e-08)	0.271 (1.00)	0.38 (1.00)	0.62 (1.00)	1 (1.00)
KRAS	58 (38%)	96	0.0241 (1.00)	0.000638 (0.0638)	0.0552 (1.00)	0.72 (1.00)	0.752 (1.00)	0.626 (1.00)	0.283 (1.00)
FBXW7	29 (19%)	125	0.227 (1.00)	0.0892 (1.00)	0.00223 (0.221)	0.00343 (0.333)	0.233 (1.00)	1 (1.00)	0.474 (1.00)
APC	103 (67%)	51	0.171 (1.00)	0.0187 (1.00)	0.025 (1.00)	0.216 (1.00)	0.388 (1.00)	0.601 (1.00)	0.258 (1.00)
PIK3CA	26 (17%)	128	0.331 (1.00)	0.336 (1.00)	0.00617 (0.592)	0.119 (1.00)	0.332 (1.00)	0.514 (1.00)	0.416 (1.00)
NRAS	15 (10%)	139	0.0773 (1.00)	0.409 (1.00)	0.927 (1.00)	0.465 (1.00)	0.332 (1.00)	1 (1.00)	1 (1.00)
SMAD4	18 (12%)	136	0.304 (1.00)	0.58 (1.00)	0.0558 (1.00)	0.852 (1.00)	0.495 (1.00)	1 (1.00)	1 (1.00)
FAM123B	19 (12%)	135	0.208 (1.00)	0.00622 (0.592)	0.0228 (1.00)	0.286 (1.00)	0.422 (1.00)	0.425 (1.00)	0.338 (1.00)
SOX9	9 (6%)	145	0.235 (1.00)	0.214 (1.00)	0.223 (1.00)	0.231 (1.00)	0.461 (1.00)	1 (1.00)	1 (1.00)
ACVR2A	8 (5%)	146	0.045 (1.00)	0.296 (1.00)	0.0382 (1.00)	0.199 (1.00)	0.668 (1.00)	1 (1.00)	0.162 (1.00)
TNFRSF10C	6 (4%)	148	0.381 (1.00)	0.676 (1.00)	0.299 (1.00)	0.68 (1.00)	0.169 (1.00)	1 (1.00)	1 (1.00)
ACOT4	3 (2%)	151	0.665 (1.00)	0.391 (1.00)	0.462 (1.00)			1 (1.00)	1 (1.00)
SMAD2	10 (6%)	144	0.0995 (1.00)	0.19 (1.00)	0.0277 (1.00)	1 (1.00)	0.377 (1.00)	1 (1.00)	1 (1.00)
PCBP1	4 (3%)	150	0.33 (1.00)	0.552 (1.00)	0.44 (1.00)			1 (1.00)	1 (1.00)
GGT1	3 (2%)	151			0.23 (1.00)			1 (1.00)	1 (1.00)

'BRAF MUTATION STATUS' versus 'MRNA_CNMF'

P value = 3.29e-07 (Fisher's exact test), Q value = 3.4e-05

Table S1. Gene #3: 'BRAF MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	34	57	28	22
BRAF MUTATED	14	1	3	0
BRAF WILD-TYPE	20	56	25	22

Figure S1. Get High-res Image Gene #3: 'BRAF MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

'BRAF MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 4.37e-08 (Fisher's exact test), Q value = 4.5e-06

Table S2. Gene #3: 'BRAF MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	53	42	46
BRAF MUTATED	1	16	1
BRAF WILD-TYPE	52	26	45

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

'BRAF MUTATION STATUS' versus 'CN_CNMF'

P value = 9.33e-05 (Fisher's exact test), Q value = 0.0094

Table S3. Gene #3: 'BRAF MUTATION STATUS' versus Clinical Feature #3: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	72	64	16
BRAF MUTATED	2	17	1
BRAF WILD-TYPE	70	47	15

Figure S3. Get High-res Image Gene #3: 'BRAF MUTATION STATUS' versus Clinical Feature #3: 'CN_CNMF'

'KRAS MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.000638 (Fisher's exact test), Q value = 0.064

Table S4. Gene #4: 'KRAS MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	53	42	46
KRAS MUTATED	27	16	7
KRAS WILD-TYPE	26	26	39

Figure S4. Get High-res Image Gene #4: 'KRAS MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

'TP53 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.00226 (Fisher's exact test), Q value = 0.22

Table S5. Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	34	57	28	22
TP53 MUTATED	12	39	9	10
TP53 WILD-TYPE	22	18	19	12

Figure S5. Get High-res Image Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

'TP53 MUTATION STATUS' versus 'CN_CNMF'

P value = 9.19e-10 (Fisher's exact test), Q value = 9.6e-08

Table S6. Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #3: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	72	64	16
TP53 MUTATED	53	13	7
TP53 WILD-TYPE	19	51	9

Figure S6. Get High-res Image Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #3: 'CN_CNMF'

'FBXW7 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.00223 (Fisher's exact test), Q value = 0.22

Table S7. Gene #6: 'FBXW7 MUTATION STATUS' versus Clinical Feature #3: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	72	64	16
FBXW7 MUTATED	6	20	3
FBXW7 WILD-TYPE	66	44	13

Figure S7. Get High-res Image Gene #6: 'FBXW7 MUTATION STATUS' versus Clinical Feature #3: 'CN_CNMF'

Methods & Data

Input

Mutation data file = COAD-TP.mutsig.cluster.txt
Molecular subtypes file = COAD-TP.transferedmergedcluster.txt
Number of patients = 154
Number of significantly mutated genes = 16
Number of Molecular subtypes = 7
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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