Correlation between gene mutation status and molecular subtypes

Rectum Adenocarcinoma (Primary solid tumor)

22 February 2013 | analyses__2013_02_22

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/C19P2ZV9

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 9 molecular subtypes across 69 patients, 3 significant findings detected with P value < 0.05 and Q value < 0.25.

KRAS mutation correlated to 'MRNASEQ_CHIERARCHICAL'.
TP53 mutation correlated to 'MRNA_CNMF' and 'MRNA_CHIERARCHICAL'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 16 genes and 9 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, 3 significant findings detected.


		Clinical Features	MRNA CNMF	MRNA CHIERARCHICAL	CN CNMF	RPPA CNMF	RPPA CHIERARCHICAL	MRNASEQ CNMF	MRNASEQ CHIERARCHICAL	MIRSEQ CNMF	MIRSEQ CHIERARCHICAL
	nMutated (%)	nWild-Type	Fisher's exact test	Fisher's exact test	Chi-square test	Fisher's exact test	Chi-square test	Fisher's exact test	Fisher's exact test	Fisher's exact test	Fisher's exact test
TP53	45 (65%)	24	0.000229 (0.0311)	0.00135 (0.181)	0.21 (1.00)	0.144 (1.00)	0.294 (1.00)	0.223 (1.00)	0.461 (1.00)	0.812 (1.00)	0.288 (1.00)
KRAS	38 (55%)	31	0.342 (1.00)	0.18 (1.00)	0.00233 (0.31)	0.737 (1.00)	0.764 (1.00)	0.00844 (1.00)	0.000835 (0.113)	0.292 (1.00)	0.0465 (1.00)
APC	57 (83%)	12	0.85 (1.00)	0.78 (1.00)	0.0561 (1.00)	0.456 (1.00)	0.647 (1.00)	0.344 (1.00)	1 (1.00)	0.337 (1.00)	1 (1.00)
SMAD4	8 (12%)	61	0.105 (1.00)	0.361 (1.00)	0.914 (1.00)	0.597 (1.00)	0.17 (1.00)	0.636 (1.00)	0.126 (1.00)	0.309 (1.00)	1 (1.00)
KIAA1804	9 (13%)	60	0.322 (1.00)	0.578 (1.00)	0.0997 (1.00)	0.795 (1.00)	0.471 (1.00)	0.712 (1.00)	0.469 (1.00)	0.805 (1.00)	1 (1.00)
FBXW7	9 (13%)	60	0.148 (1.00)	0.0962 (1.00)	0.409 (1.00)	0.148 (1.00)	0.855 (1.00)	0.185 (1.00)	0.0626 (1.00)	0.805 (1.00)	1 (1.00)
NRAS	5 (7%)	64	0.856 (1.00)	1 (1.00)	0.675 (1.00)			0.532 (1.00)	0.716 (1.00)	0.0969 (1.00)	1 (1.00)
TCF7L2	7 (10%)	62	0.883 (1.00)	0.683 (1.00)	0.709 (1.00)	0.169 (1.00)	0.461 (1.00)	0.224 (1.00)	0.315 (1.00)	1 (1.00)	1 (1.00)
PIK3CA	7 (10%)	62	1 (1.00)	0.731 (1.00)	0.814 (1.00)	0.356 (1.00)	0.556 (1.00)	0.866 (1.00)	0.587 (1.00)	0.343 (1.00)	0.328 (1.00)
OPCML	6 (9%)	63	0.228 (1.00)	0.0972 (1.00)	0.508 (1.00)	0.169 (1.00)	0.628 (1.00)	0.942 (1.00)	0.749 (1.00)	1 (1.00)	1 (1.00)
SMAD2	5 (7%)	64	1 (1.00)	1 (1.00)	0.29 (1.00)	0.0155 (1.00)	0.291 (1.00)	0.369 (1.00)	0.154 (1.00)	1 (1.00)	1 (1.00)
SPATA8	3 (4%)	66			0.388 (1.00)			0.694 (1.00)	0.439 (1.00)	0.432 (1.00)	0.176 (1.00)
ERBB2	4 (6%)	65	0.54 (1.00)	1 (1.00)	0.576 (1.00)	0.0567 (1.00)	0.628 (1.00)	0.614 (1.00)	0.6 (1.00)	1 (1.00)	1 (1.00)
IL1RAPL2	5 (7%)	64	0.613 (1.00)	0.519 (1.00)	0.785 (1.00)			0.473 (1.00)	0.524 (1.00)	0.273 (1.00)	1 (1.00)
FAM123B	6 (9%)	63	1 (1.00)	0.731 (1.00)	0.463 (1.00)	0.243 (1.00)	0.375 (1.00)	0.358 (1.00)	0.3 (1.00)	1 (1.00)	1 (1.00)
ZIM3	5 (7%)	64	0.827 (1.00)	0.668 (1.00)	0.433 (1.00)	0.00342 (0.451)	0.185 (1.00)	0.445 (1.00)	0.524 (1.00)	0.387 (1.00)	0.28 (1.00)

'KRAS MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.000835 (Fisher's exact test), Q value = 0.11

Table S1. Gene #2: 'KRAS MUTATION STATUS' versus Clinical Feature #7: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	15	24	28
KRAS MUTATED	9	19	8
KRAS WILD-TYPE	6	5	20

Figure S1. Get High-res Image Gene #2: 'KRAS MUTATION STATUS' versus Clinical Feature #7: 'MRNASEQ_CHIERARCHICAL'

'TP53 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.000229 (Fisher's exact test), Q value = 0.031

Table S2. Gene #3: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	24	19	21
TP53 MUTATED	8	13	19
TP53 WILD-TYPE	16	6	2

Figure S2. Get High-res Image Gene #3: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'MRNA_CNMF'

'TP53 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.00135 (Fisher's exact test), Q value = 0.18

Table S3. Gene #3: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	17	23	24
TP53 MUTATED	15	8	17
TP53 WILD-TYPE	2	15	7

Figure S3. Get High-res Image Gene #3: 'TP53 MUTATION STATUS' versus Clinical Feature #2: 'MRNA_CHIERARCHICAL'

Methods & Data

Input

Mutation data file = READ-TP.mutsig.cluster.txt
Molecular subtypes file = READ-TP.transferedmergedcluster.txt
Number of patients = 69
Number of significantly mutated genes = 16
Number of Molecular subtypes = 9
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

Chi-square test

For multi-class clinical features (nominal or ordinal), Chi-square tests (Greenwood and Nikulin 1996) were used to estimate the P values using the 'chisq.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] Greenwood and Nikulin, A guide to chi-squared testing, Wiley, New York. ISBN 047155779X (1996)

[3] 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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