Correlation between gene mutation status and molecular subtypes
Cervical Squamous Cell Carcinoma and Endocervical 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/C15M6433
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 Chi-square 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 0.0309
(0.927)
0.461
(1.00)
0.422
(1.00)
0.687
(1.00)
0.677
(1.00)
0.431
(1.00)
1
(1.00)
0.627
(1.00)
TMCC1 4 (10%) 35 0.397
(1.00)
0.736
(1.00)
1
(1.00)
1
(1.00)
0.8
(1.00)
0.589
(1.00)
0.257
(1.00)
UGT3A2 3 (8%) 36 0.881
(1.00)
0.118
(1.00)
0.343
(1.00)
1
(1.00)
0.52
(1.00)
1
(1.00)
0.42
(1.00)
MAPK1 3 (8%) 36 0.0426
(1.00)
0.647
(1.00)
0.667
(1.00)
1
(1.00)
0.407
(1.00)
1
(1.00)
1
(1.00)
0.672
(1.00)
'PIK3CA MUTATION STATUS' versus 'CN_CNMF'

P value = 0.0309 (Fisher's exact test), Q value = 0.93

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

nPatients CLUS_1 CLUS_2 CLUS_3
ALL 15 9 12
PIK3CA MUTATED 3 0 6
PIK3CA WILD-TYPE 12 9 6

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 = 0.461 (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 11 6 7 7 5 1 2
PIK3CA MUTATED 4 0 3 1 1 0 0
PIK3CA WILD-TYPE 7 6 4 6 4 1 2
'PIK3CA MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.422 (Chi-square 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 CLUS_5
ALL 15 5 5 7 6
PIK3CA MUTATED 5 1 2 0 1
PIK3CA WILD-TYPE 10 4 3 7 5
'PIK3CA MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.687 (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 6 4 28
PIK3CA MUTATED 1 0 8
PIK3CA WILD-TYPE 5 4 20
'PIK3CA MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.677 (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 21 6 12
PIK3CA MUTATED 4 2 3
PIK3CA WILD-TYPE 17 4 9
'PIK3CA MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.431 (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 CLUS_4
ALL 19 8 6 6
PIK3CA MUTATED 6 1 2 0
PIK3CA WILD-TYPE 13 7 4 6
'PIK3CA MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 1 (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 26 6 7
PIK3CA MUTATED 6 1 2
PIK3CA WILD-TYPE 20 5 5
'PIK3CA MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.627 (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 4 25 10
PIK3CA MUTATED 0 6 3
PIK3CA WILD-TYPE 4 19 7
'TMCC1 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.397 (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 11 6 7 7 5 1 2
TMCC1 MUTATED 3 1 0 0 0 0 0
TMCC1 WILD-TYPE 8 5 7 7 5 1 2
'TMCC1 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.736 (Chi-square 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 CLUS_5
ALL 15 5 5 7 6
TMCC1 MUTATED 2 0 1 1 0
TMCC1 WILD-TYPE 13 5 4 6 6
'TMCC1 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 1 (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 6 4 28
TMCC1 MUTATED 0 0 4
TMCC1 WILD-TYPE 6 4 24
'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 21 6 12
TMCC1 MUTATED 3 0 1
TMCC1 WILD-TYPE 18 6 11
'TMCC1 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.8 (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 CLUS_4
ALL 19 8 6 6
TMCC1 MUTATED 3 1 0 0
TMCC1 WILD-TYPE 16 7 6 6
'TMCC1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 0.589 (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 26 6 7
TMCC1 MUTATED 4 0 0
TMCC1 WILD-TYPE 22 6 7
'TMCC1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.257 (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 4 25 10
TMCC1 MUTATED 1 3 0
TMCC1 WILD-TYPE 3 22 10
'UGT3A2 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.881 (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 11 6 7 7 5 1 2
UGT3A2 MUTATED 1 1 0 1 0 0 0
UGT3A2 WILD-TYPE 10 5 7 6 5 1 2
'UGT3A2 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.118 (Chi-square 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 CLUS_5
ALL 15 5 5 7 6
UGT3A2 MUTATED 0 0 1 2 0
UGT3A2 WILD-TYPE 15 5 4 5 6
'UGT3A2 MUTATION STATUS' versus 'MRNASEQ_CHIERARCHICAL'

P value = 0.343 (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 6 4 28
UGT3A2 MUTATED 0 1 2
UGT3A2 WILD-TYPE 6 3 26
'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 21 6 12
UGT3A2 MUTATED 2 0 1
UGT3A2 WILD-TYPE 19 6 11
'UGT3A2 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.52 (Fisher's exact test), Q value = 1

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

nPatients CLUS_1 CLUS_2 CLUS_3 CLUS_4
ALL 19 8 6 6
UGT3A2 MUTATED 1 1 0 1
UGT3A2 WILD-TYPE 18 7 6 5
'UGT3A2 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 1 (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 26 6 7
UGT3A2 MUTATED 3 0 0
UGT3A2 WILD-TYPE 23 6 7
'UGT3A2 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.42 (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 4 25 10
UGT3A2 MUTATED 1 2 0
UGT3A2 WILD-TYPE 3 23 10
'MAPK1 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.0426 (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 15 9 12
MAPK1 MUTATED 0 0 3
MAPK1 WILD-TYPE 15 9 9

Figure S2.  Get High-res Image Gene #4: 'MAPK1 MUTATION STATUS' versus Molecular Subtype #1: 'CN_CNMF'

'MAPK1 MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 0.647 (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 11 6 7 7 5 1 2
MAPK1 MUTATED 2 1 0 0 0 0 0
MAPK1 WILD-TYPE 9 5 7 7 5 1 2
'MAPK1 MUTATION STATUS' versus 'MRNASEQ_CNMF'

P value = 0.667 (Chi-square 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 CLUS_5
ALL 15 5 5 7 6
MAPK1 MUTATED 1 0 1 1 0
MAPK1 WILD-TYPE 14 5 4 6 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 6 4 28
MAPK1 MUTATED 0 0 3
MAPK1 WILD-TYPE 6 4 25
'MAPK1 MUTATION STATUS' versus 'MIRSEQ_CNMF'

P value = 0.407 (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 21 6 12
MAPK1 MUTATED 3 0 0
MAPK1 WILD-TYPE 18 6 12
'MAPK1 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 1 (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 CLUS_4
ALL 19 8 6 6
MAPK1 MUTATED 2 1 0 0
MAPK1 WILD-TYPE 17 7 6 6
'MAPK1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CNMF'

P value = 1 (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 26 6 7
MAPK1 MUTATED 3 0 0
MAPK1 WILD-TYPE 23 6 7
'MAPK1 MUTATION STATUS' versus 'MIRSEQ_MATURE_CHIERARCHICAL'

P value = 0.672 (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 4 25 10
MAPK1 MUTATED 0 3 0
MAPK1 WILD-TYPE 4 22 10
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.

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)