Correlation between gene mutation status and molecular subtypes
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (Primary solid tumor)
16 April 2014 | analyses__2014_04_16
Maintainer Information
Citation Information
doi:10.7908/C1DJ5D79
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/C1DJ5D79
Overview
Introduction

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

Summary

Testing the association between mutation status of 4 genes and 8 molecular subtypes across 39 patients, no significant finding detected with P value < 0.05 and Q value < 0.25.

- No gene mutations related to molecuar subtypes.

Results
Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 4 genes and 8 molecular subtypes. Shown in the table are P values (Q values). Thresholded by P value < 0.05 and Q value < 0.25, no significant finding detected.

|  | Clinical Features | CN CNMF | METHLYATION CNMF | MRNASEQ CNMF | MRNASEQ CHIERARCHICAL | MIRSEQ CNMF | MIRSEQ CHIERARCHICAL | MIRSEQ MATURE CNMF | MIRSEQ MATURE CHIERARCHICAL
| nMutated (%) | nWild-Type | Fisher's exact test | Chi-square 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
PIK3CA | 9 (23%) | 30 | 0.0461 (1.00) | 0.469 (1.00) | 0.25 (1.00) | 0.799 (1.00) | 0.874 (1.00) | 0.0741 (1.00) | 0.737 (1.00) | 0.524 (1.00)
TMCC1 | 4 (10%) | 35 |  | 0.481 (1.00) | 0.703 (1.00) | 0.653 (1.00) | 1 (1.00) | 0.349 (1.00) | 0.435 (1.00) | 1 (1.00)
UGT3A2 | 3 (8%) | 36 |  | 0.855 (1.00) | 0.051 (1.00) | 1 (1.00) | 1 (1.00) | 0.0263 (0.788) | 0.698 (1.00) | 0.0881 (1.00)
MAPK1 | 3 (8%) | 36 | 0.0518 (1.00) | 0.705 (1.00) | 1 (1.00) | 1 (1.00) | 0.388 (1.00) | 0.792 (1.00) | 0.698 (1.00) | 1 (1.00)

'PIK3CA MUTATION STATUS' versus 'CN_CNMF'

P value = 0.0461 (Fisher's exact test), Q value = 1

Table S1. Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 14 | 9 | 13
PIK3CA MUTATED | 3 | 0 | 6
PIK3CA WILD-TYPE | 11 | 9 | 7

Figure S1. Get High-res Image Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

'PIK3CA MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.469 (Chi-square test), Q value = 1

Table S2. Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6 | CLUS_7
--- | --- | --- | --- | --- | --- | --- | ---
ALL | 12 | 7 | 2 | 6 | 6 | 4 | 2
PIK3CA MUTATED | 5 | 2 | 0 | 0 | 1 | 1 | 0
PIK3CA WILD-TYPE | 7 | 5 | 2 | 6 | 5 | 3 | 2

'PIK3CA MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.25 (Fisher's exact test), Q value = 1

Table S3. Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 19 | 5 | 7 | 7
PIK3CA MUTATED | 7 | 1 | 1 | 0
PIK3CA WILD-TYPE | 12 | 4 | 6 | 7

'PIK3CA MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.799 (Fisher's exact test), Q value = 1

Table S4. Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 2 | 29 | 7
PIK3CA MUTATED | 0 | 8 | 1
PIK3CA WILD-TYPE | 2 | 21 | 6

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.874 (Fisher's exact test), Q value = 1

Table S5. Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 20 | 6 | 13
PIK3CA MUTATED | 4 | 2 | 3
PIK3CA WILD-TYPE | 16 | 4 | 10

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.0741 (Fisher's exact test), Q value = 1

Table S6. Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 19 | 10 | 10
PIK3CA MUTATED | 7 | 0 | 2
PIK3CA WILD-TYPE | 12 | 10 | 8

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.737 (Fisher's exact test), Q value = 1

Table S7. Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 24 | 5 | 10
PIK3CA MUTATED | 5 | 2 | 2
PIK3CA WILD-TYPE | 19 | 3 | 8

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.524 (Fisher's exact test), Q value = 1

Table S8. Gene #1: 'PIK3CA MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 19 | 15 | 5
PIK3CA MUTATED | 6 | 2 | 1
PIK3CA WILD-TYPE | 13 | 13 | 4

'TMCC1 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.481 (Chi-square test), Q value = 1

Table S9. Gene #2: 'TMCC1 MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6 | CLUS_7
--- | --- | --- | --- | --- | --- | --- | ---
ALL | 12 | 7 | 2 | 6 | 6 | 4 | 2
TMCC1 MUTATED | 3 | 0 | 0 | 1 | 0 | 0 | 0
TMCC1 WILD-TYPE | 9 | 7 | 2 | 5 | 6 | 4 | 2

'TMCC1 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.703 (Fisher's exact test), Q value = 1

Table S10. Gene #2: 'TMCC1 MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 19 | 5 | 7 | 7
TMCC1 MUTATED | 2 | 1 | 0 | 1
TMCC1 WILD-TYPE | 17 | 4 | 7 | 6

'TMCC1 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.653 (Fisher's exact test), Q value = 1

Table S11. Gene #2: 'TMCC1 MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 2 | 29 | 7
TMCC1 MUTATED | 0 | 4 | 0
TMCC1 WILD-TYPE | 2 | 25 | 7

'TMCC1 MUTATION STATUS' versus 'MIRSEQ_CNMF'

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

Table S12. Gene #2: 'TMCC1 MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 20 | 6 | 13
TMCC1 MUTATED | 3 | 0 | 1
TMCC1 WILD-TYPE | 17 | 6 | 12

'TMCC1 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.349 (Fisher's exact test), Q value = 1

Table S13. Gene #2: 'TMCC1 MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 19 | 10 | 10
TMCC1 MUTATED | 2 | 2 | 0
TMCC1 WILD-TYPE | 17 | 8 | 10

'TMCC1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.435 (Fisher's exact test), Q value = 1

Table S14. Gene #2: 'TMCC1 MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 24 | 5 | 10
TMCC1 MUTATED | 4 | 0 | 0
TMCC1 WILD-TYPE | 20 | 5 | 10

'TMCC1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

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

Table S15. Gene #2: 'TMCC1 MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 19 | 15 | 5
TMCC1 MUTATED | 2 | 2 | 0
TMCC1 WILD-TYPE | 17 | 13 | 5

'UGT3A2 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.855 (Chi-square test), Q value = 1

Table S16. Gene #3: 'UGT3A2 MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6 | CLUS_7
--- | --- | --- | --- | --- | --- | --- | ---
ALL | 12 | 7 | 2 | 6 | 6 | 4 | 2
UGT3A2 MUTATED | 1 | 0 | 0 | 1 | 1 | 0 | 0
UGT3A2 WILD-TYPE | 11 | 7 | 2 | 5 | 5 | 4 | 2

'UGT3A2 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.051 (Fisher's exact test), Q value = 1

Table S17. Gene #3: 'UGT3A2 MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 19 | 5 | 7 | 7
UGT3A2 MUTATED | 0 | 1 | 0 | 2
UGT3A2 WILD-TYPE | 19 | 4 | 7 | 5

'UGT3A2 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

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

Table S18. Gene #3: 'UGT3A2 MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 2 | 29 | 7
UGT3A2 MUTATED | 0 | 3 | 0
UGT3A2 WILD-TYPE | 2 | 26 | 7

'UGT3A2 MUTATION STATUS' versus 'MIRSEQ_CNMF'

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

Table S19. Gene #3: 'UGT3A2 MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 20 | 6 | 13
UGT3A2 MUTATED | 2 | 0 | 1
UGT3A2 WILD-TYPE | 18 | 6 | 12

'UGT3A2 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.0263 (Fisher's exact test), Q value = 0.79

Table S20. Gene #3: 'UGT3A2 MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 19 | 10 | 10
UGT3A2 MUTATED | 0 | 3 | 0
UGT3A2 WILD-TYPE | 19 | 7 | 10

Figure S2. Get High-res Image Gene #3: 'UGT3A2 MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

'UGT3A2 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.698 (Fisher's exact test), Q value = 1

Table S21. Gene #3: 'UGT3A2 MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 24 | 5 | 10
UGT3A2 MUTATED | 3 | 0 | 0
UGT3A2 WILD-TYPE | 21 | 5 | 10

'UGT3A2 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.0881 (Fisher's exact test), Q value = 1

Table S22. Gene #3: 'UGT3A2 MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 19 | 15 | 5
UGT3A2 MUTATED | 0 | 3 | 0
UGT3A2 WILD-TYPE | 19 | 12 | 5

'MAPK1 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.0518 (Fisher's exact test), Q value = 1

Table S23. Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 14 | 9 | 13
MAPK1 MUTATED | 0 | 0 | 3
MAPK1 WILD-TYPE | 14 | 9 | 10

'MAPK1 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.705 (Chi-square test), Q value = 1

Table S24. Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #2: 'METHLYATION_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4 | CLUS_5 | CLUS_6 | CLUS_7
--- | --- | --- | --- | --- | --- | --- | ---
ALL | 12 | 7 | 2 | 6 | 6 | 4 | 2
MAPK1 MUTATED | 2 | 0 | 0 | 1 | 0 | 0 | 0
MAPK1 WILD-TYPE | 10 | 7 | 2 | 5 | 6 | 4 | 2

'MAPK1 MUTATION STATUS' versus 'MRNASEQ_CNMF'

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

Table S25. Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #3: 'MRNASEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3 | CLUS_4
--- | --- | --- | --- | ---
ALL | 19 | 5 | 7 | 7
MAPK1 MUTATED | 2 | 0 | 0 | 1
MAPK1 WILD-TYPE | 17 | 5 | 7 | 6

'MAPK1 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

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

Table S26. Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #4: 'MRNASEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 2 | 29 | 7
MAPK1 MUTATED | 0 | 3 | 0
MAPK1 WILD-TYPE | 2 | 26 | 7

'MAPK1 MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.388 (Fisher's exact test), Q value = 1

Table S27. Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #5: 'MIRSEQ_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 20 | 6 | 13
MAPK1 MUTATED | 3 | 0 | 0
MAPK1 WILD-TYPE | 17 | 6 | 13

'MAPK1 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.792 (Fisher's exact test), Q value = 1

Table S28. Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #6: 'MIRSEQ_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 19 | 10 | 10
MAPK1 MUTATED | 2 | 1 | 0
MAPK1 WILD-TYPE | 17 | 9 | 10

'MAPK1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.698 (Fisher's exact test), Q value = 1

Table S29. Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #7: 'MIRSEQ_MATURE_CNMF'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 24 | 5 | 10
MAPK1 MUTATED | 3 | 0 | 0
MAPK1 WILD-TYPE | 21 | 5 | 10

'MAPK1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

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

Table S30. Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #8: 'MIRSEQ_MATURE_CHIERARCHICAL'

nPatients | CLUS_1 | CLUS_2 | CLUS_3
--- | --- | --- | ---
ALL | 19 | 15 | 5
MAPK1 MUTATED | 2 | 1 | 0
MAPK1 WILD-TYPE | 17 | 14 | 5

Methods & Data
Input

- Mutation data file = transformed.cor.cli.txt

- Molecular subtypes file = CESC-TP.transferedmergedcluster.txt

- Number of patients = 39

- Number of significantly mutated genes = 4

- Number of Molecular subtypes = 8

- 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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

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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