Correlation between gene mutation status and molecular subtypes

Rectum Adenocarcinoma (Primary solid tumor)

15 January 2014 | analyses__2014_01_15

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 (2014): Correlation between gene mutation status and molecular subtypes. Broad Institute of MIT and Harvard. doi:10.7908/C1BG2MGG

Overview

Introduction

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

Summary

Testing the association between mutation status of 3 genes and 9 molecular subtypes across 69 patients, 4 significant findings detected with P value < 0.05 and Q value < 0.25.

KRAS mutation correlated to 'MRNA_CHIERARCHICAL' and 'CN_CNMF'.
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 3 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, 4 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
KRAS	38 (55%)	31	0.262 (1.00)	0.00629 (0.151)	0.00169 (0.0439)	0.78 (1.00)	0.817 (1.00)	0.0269 (0.619)	1 (1.00)	0.292 (1.00)	0.0465 (1.00)
TP53	45 (65%)	24	0.000442 (0.0119)	0.00311 (0.0777)	0.348 (1.00)	0.167 (1.00)	0.603 (1.00)	0.177 (1.00)	0.755 (1.00)	0.812 (1.00)	0.288 (1.00)
APC	57 (83%)	12	0.568 (1.00)	0.849 (1.00)	0.227 (1.00)	0.362 (1.00)	0.598 (1.00)	1 (1.00)	0.27 (1.00)	0.337 (1.00)	1 (1.00)

'APC MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.568 (Fisher's exact test), Q value = 1

Table S1. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	24	21	19
APC MUTATED	19	16	17
APC WILD-TYPE	5	5	2

'APC MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.849 (Fisher's exact test), Q value = 1

Table S2. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	23	26	15
APC MUTATED	18	22	12
APC WILD-TYPE	5	4	3

'APC MUTATION STATUS' versus 'CN_CNMF'

P value = 0.227 (Chi-square test), Q value = 1

Table S3. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #3: 'CN_CNMF'

nPatients	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6
ALL	17	18	17	11	5
APC MUTATED	11	16	15	9	5
APC WILD-TYPE	6	2	2	2	0

'APC MUTATION STATUS' versus 'RPPA_CNMF'

P value = 0.362 (Fisher's exact test), Q value = 1

Table S4. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #4: 'RPPA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	16	14	23
APC MUTATED	11	12	20
APC WILD-TYPE	5	2	3

'APC MUTATION STATUS' versus 'RPPA_CHIERARCHICAL'

P value = 0.598 (Chi-square test), Q value = 1

Table S5. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #5: 'RPPA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	2	4	12	21	14
APC MUTATED	1	3	11	16	12
APC WILD-TYPE	1	1	1	5	2

'APC MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 1 (Fisher's exact test), Q value = 1

Table S6. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #6: 'MRNASEQ_CNMF'

nPatients	CLUS_2	CLUS_3
ALL	6	61
APC MUTATED	5	51
APC WILD-TYPE	1	10

'APC MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.27 (Fisher's exact test), Q value = 1

Table S7. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #7: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_4
ALL	62	4	1
APC MUTATED	53	2	1
APC WILD-TYPE	9	2	0

'APC MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.337 (Fisher's exact test), Q value = 1

Table S8. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_3	CLUS_4	CLUS_5
ALL	2	3	6	54
APC MUTATED	1	3	6	45
APC WILD-TYPE	1	0	0	9

'APC MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 1 (Fisher's exact test), Q value = 1

Table S9. Gene #1: 'APC MUTATION STATUS' versus Molecular Subtype #9: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2
ALL	4	61
APC MUTATED	4	51
APC WILD-TYPE	0	10

'KRAS MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.262 (Fisher's exact test), Q value = 1

Table S10. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	24	21	19
KRAS MUTATED	16	11	8
KRAS WILD-TYPE	8	10	11

'KRAS MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.00629 (Fisher's exact test), Q value = 0.15

Table S11. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	23	26	15
KRAS MUTATED	16	8	11
KRAS WILD-TYPE	7	18	4

Figure S1. Get High-res Image Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

'KRAS MUTATION STATUS' versus 'CN_CNMF'

P value = 0.00169 (Chi-square test), Q value = 0.044

Table S12. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #3: 'CN_CNMF'

nPatients	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6
ALL	17	18	17	11	5
KRAS MUTATED	3	13	9	8	5
KRAS WILD-TYPE	14	5	8	3	0

Figure S2. Get High-res Image Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #3: 'CN_CNMF'

'KRAS MUTATION STATUS' versus 'RPPA_CNMF'

P value = 0.78 (Fisher's exact test), Q value = 1

Table S13. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #4: 'RPPA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	16	14	23
KRAS MUTATED	7	8	12
KRAS WILD-TYPE	9	6	11

'KRAS MUTATION STATUS' versus 'RPPA_CHIERARCHICAL'

P value = 0.817 (Chi-square test), Q value = 1

Table S14. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #5: 'RPPA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	2	4	12	21	14
KRAS MUTATED	1	2	6	9	9
KRAS WILD-TYPE	1	2	6	12	5

'KRAS MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.0269 (Fisher's exact test), Q value = 0.62

Table S15. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #6: 'MRNASEQ_CNMF'

nPatients	CLUS_2	CLUS_3
ALL	6	61
KRAS MUTATED	6	30
KRAS WILD-TYPE	0	31

Figure S3. Get High-res Image Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #6: 'MRNASEQ_CNMF'

'KRAS MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1 (Fisher's exact test), Q value = 1

Table S16. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #7: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_4
ALL	62	4	1
KRAS MUTATED	33	2	1
KRAS WILD-TYPE	29	2	0

'KRAS MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.292 (Fisher's exact test), Q value = 1

Table S17. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_3	CLUS_4	CLUS_5
ALL	2	3	6	54
KRAS MUTATED	1	2	1	30
KRAS WILD-TYPE	1	1	5	24

'KRAS MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.0465 (Fisher's exact test), Q value = 1

Table S18. Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #9: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2
ALL	4	61
KRAS MUTATED	0	34
KRAS WILD-TYPE	4	27

Figure S4. Get High-res Image Gene #2: 'KRAS MUTATION STATUS' versus Molecular Subtype #9: 'MIRSEQ_CHIERARCHICAL'

'TP53 MUTATION STATUS' versus 'MRNA_CNMF'

P value = 0.000442 (Fisher's exact test), Q value = 0.012

Table S19. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	24	21	19
TP53 MUTATED	8	15	17
TP53 WILD-TYPE	16	6	2

Figure S5. Get High-res Image Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #1: 'MRNA_CNMF'

'TP53 MUTATION STATUS' versus 'MRNA_CHIERARCHICAL'

P value = 0.00311 (Fisher's exact test), Q value = 0.078

Table S20. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	23	26	15
TP53 MUTATED	8	20	12
TP53 WILD-TYPE	15	6	3

Figure S6. Get High-res Image Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #2: 'MRNA_CHIERARCHICAL'

'TP53 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.348 (Chi-square test), Q value = 1

Table S21. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #3: 'CN_CNMF'

nPatients	CLUS_2	CLUS_3	CLUS_4	CLUS_5	CLUS_6
ALL	17	18	17	11	5
TP53 MUTATED	13	9	10	9	3
TP53 WILD-TYPE	4	9	7	2	2

'TP53 MUTATION STATUS' versus 'RPPA_CNMF'

P value = 0.167 (Fisher's exact test), Q value = 1

Table S22. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #4: 'RPPA_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	16	14	23
TP53 MUTATED	10	12	13
TP53 WILD-TYPE	6	2	10

'TP53 MUTATION STATUS' versus 'RPPA_CHIERARCHICAL'

P value = 0.603 (Chi-square test), Q value = 1

Table S23. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #5: 'RPPA_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4	CLUS_5
ALL	2	4	12	21	14
TP53 MUTATED	1	3	10	12	9
TP53 WILD-TYPE	1	1	2	9	5

'TP53 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.177 (Fisher's exact test), Q value = 1

Table S24. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #6: 'MRNASEQ_CNMF'

nPatients	CLUS_2	CLUS_3
ALL	6	61
TP53 MUTATED	2	41
TP53 WILD-TYPE	4	20

'TP53 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.755 (Fisher's exact test), Q value = 1

Table S25. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #7: 'MRNASEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_4
ALL	62	4	1
TP53 MUTATED	40	2	1
TP53 WILD-TYPE	22	2	0

'TP53 MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.812 (Fisher's exact test), Q value = 1

Table S26. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_CNMF'

nPatients	CLUS_1	CLUS_3	CLUS_4	CLUS_5
ALL	2	3	6	54
TP53 MUTATED	1	2	5	34
TP53 WILD-TYPE	1	1	1	20

'TP53 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.288 (Fisher's exact test), Q value = 1

Table S27. Gene #3: 'TP53 MUTATION STATUS' versus Molecular Subtype #9: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2
ALL	4	61
TP53 MUTATED	4	38
TP53 WILD-TYPE	0	23

Methods & Data

Input

Mutation data file = transformed.cor.cli.txt
Molecular subtypes file = READ-TP.transferedmergedcluster.txt
Number of patients = 69
Number of significantly mutated genes = 3
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

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] 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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