Correlation between gene mutation status and molecular subtypes

Colon Adenocarcinoma (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/C1HT2MBP

Overview

Introduction

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

Summary

Testing the association between mutation status of 15 genes and 7 molecular subtypes across 155 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 15 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%)	135	3.29e-07 (3.26e-05)	4.37e-08 (4.37e-06)	8.5e-05 (0.00833)	0.734 (1.00)	0.926 (1.00)	0.145 (1.00)	1 (1.00)
TP53	75 (48%)	80	0.00226 (0.215)	0.013 (1.00)	1.08e-09 (1.09e-07)	0.403 (1.00)	0.38 (1.00)	0.366 (1.00)	0.807 (1.00)
KRAS	58 (37%)	97	0.0241 (1.00)	0.000638 (0.0619)	0.15 (1.00)	0.772 (1.00)	0.752 (1.00)	1 (1.00)	0.613 (1.00)
FBXW7	29 (19%)	126	0.227 (1.00)	0.0892 (1.00)	0.000825 (0.0792)	0.00533 (0.501)	0.233 (1.00)	0.583 (1.00)	0.657 (1.00)
APC	103 (66%)	52	0.171 (1.00)	0.0187 (1.00)	0.101 (1.00)	0.7 (1.00)	0.388 (1.00)	1 (1.00)	1 (1.00)
PIK3CA	26 (17%)	129	0.331 (1.00)	0.336 (1.00)	0.0178 (1.00)	0.218 (1.00)	0.332 (1.00)	1 (1.00)	0.592 (1.00)
NRAS	15 (10%)	140	0.0773 (1.00)	0.409 (1.00)	0.531 (1.00)	0.0659 (1.00)	0.332 (1.00)	1 (1.00)	1 (1.00)
SMAD4	18 (12%)	137	0.304 (1.00)	0.58 (1.00)	0.01 (0.921)	0.4 (1.00)	0.495 (1.00)	1 (1.00)	1 (1.00)
FAM123B	19 (12%)	136	0.208 (1.00)	0.00622 (0.578)	0.019 (1.00)	0.579 (1.00)	0.422 (1.00)	0.498 (1.00)	0.498 (1.00)
SOX9	9 (6%)	146	0.235 (1.00)	0.214 (1.00)	0.585 (1.00)	0.14 (1.00)	0.461 (1.00)	1 (1.00)	1 (1.00)
ACVR2A	8 (5%)	147	0.045 (1.00)	0.296 (1.00)	0.098 (1.00)	0.167 (1.00)	0.668 (1.00)	1 (1.00)	0.255 (1.00)
TNFRSF10C	6 (4%)	149	0.381 (1.00)	0.676 (1.00)	0.0811 (1.00)	0.618 (1.00)	0.169 (1.00)	1 (1.00)	1 (1.00)
SMAD2	10 (6%)	145	0.0995 (1.00)	0.19 (1.00)	0.0333 (1.00)	0.943 (1.00)	0.377 (1.00)	0.283 (1.00)	1 (1.00)
ACOT4	3 (2%)	152	0.665 (1.00)	0.391 (1.00)	0.736 (1.00)			1 (1.00)	1 (1.00)
PCBP1	4 (3%)	151	0.33 (1.00)	0.552 (1.00)	0.486 (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 = 3.3e-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 = 4.4e-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 = 8.5e-05 (Fisher's exact test), Q value = 0.0083

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

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	70	64	11	8
BRAF MUTATED	2	18	0	0
BRAF WILD-TYPE	68	46	11	8

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 = 0.062

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 = 0.21

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 = 1.08e-09 (Fisher's exact test), Q value = 1.1e-07

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

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	70	64	11	8
TP53 MUTATED	51	13	4	6
TP53 WILD-TYPE	19	51	7	2

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 = 0.000825 (Fisher's exact test), Q value = 0.079

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

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	70	64	11	8
FBXW7 MUTATED	6	20	0	3
FBXW7 WILD-TYPE	64	44	11	5

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 = 155
Number of significantly mutated genes = 15
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

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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