Stomach Adenocarcinoma: Correlation between gene mutation status and molecular subtypes<BR>(primary solid tumor cohort)

Stomach Adenocarcinoma: Correlation between gene mutation status and molecular subtypes
(primary solid tumor cohort)

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Overview

Introduction

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

Summary

Testing the association between mutation status of 47 genes and 6 molecular subtypes across 116 patients, 7 significant findings detected with P value < 0.05 and Q value < 0.25.

TP53 mutation correlated to 'CN_CNMF' and 'MIRSEQ_CHIERARCHICAL'.
PIK3CA mutation correlated to 'METHLYATION_CNMF' and 'MIRSEQ_CHIERARCHICAL'.
ACVR2A mutation correlated to 'CN_CNMF'.
ARID1A mutation correlated to 'CN_CNMF' and 'MIRSEQ_CHIERARCHICAL'.

Results

Overview of the results

Table 1. Get Full Table Overview of the association between mutation status of 47 genes and 6 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	CN CNMF	METHLYATION CNMF	MRNASEQ CNMF	MRNASEQ 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
TP53	52 (45%)	64	0.000271 (0.0695)	0.011 (1.00)	1 (1.00)	0.236 (1.00)	0.00526 (1.00)	3.69e-05 (0.00951)
PIK3CA	24 (21%)	92	0.00687 (1.00)	1.26e-06 (0.000327)	0.412 (1.00)	0.84 (1.00)	0.0857 (1.00)	0.000704 (0.178)
ARID1A	22 (19%)	94	0.00027 (0.0695)	0.00783 (1.00)	0.488 (1.00)	0.274 (1.00)	0.00562 (1.00)	0.000467 (0.119)
ACVR2A	13 (11%)	103	0.000643 (0.163)	0.0128 (1.00)	0.698 (1.00)	0.424 (1.00)	0.0246 (1.00)	0.0563 (1.00)
CBWD1	14 (12%)	102	0.0053 (1.00)	0.0585 (1.00)	0.457 (1.00)	0.213 (1.00)	0.0561 (1.00)	0.193 (1.00)
KRAS	14 (12%)	102	0.182 (1.00)	0.292 (1.00)	1 (1.00)	0.299 (1.00)	0.271 (1.00)	0.706 (1.00)
PGM5	16 (14%)	100	0.0169 (1.00)	0.00266 (0.665)	0.281 (1.00)	0.157 (1.00)	0.262 (1.00)	0.162 (1.00)
RPL22	9 (8%)	107	0.0908 (1.00)		0.412 (1.00)	0.0729 (1.00)	0.282 (1.00)	0.28 (1.00)
TRIM48	10 (9%)	106	0.0671 (1.00)	0.174 (1.00)	1 (1.00)	1 (1.00)	0.103 (1.00)	0.173 (1.00)
XPOT	6 (5%)	110	0.0797 (1.00)		0.345 (1.00)	1 (1.00)	0.327 (1.00)	0.0539 (1.00)
RHOA	7 (6%)	109	0.469 (1.00)	0.639 (1.00)	0.488 (1.00)		0.383 (1.00)	0.683 (1.00)
OR8H3	10 (9%)	106	0.053 (1.00)	0.0884 (1.00)	0.108 (1.00)	0.101 (1.00)	0.873 (1.00)	0.205 (1.00)
EDNRB	12 (10%)	104	0.523 (1.00)	0.543 (1.00)	0.412 (1.00)	0.84 (1.00)	0.405 (1.00)	0.162 (1.00)
ZNF804B	18 (16%)	98	0.233 (1.00)	0.047 (1.00)	0.281 (1.00)	0.885 (1.00)	0.177 (1.00)	0.209 (1.00)
IRF2	8 (7%)	108	0.0222 (1.00)	0.0511 (1.00)	1 (1.00)	0.279 (1.00)	0.197 (1.00)	0.278 (1.00)
IAPP	4 (3%)	112	0.783 (1.00)		1 (1.00)		0.131 (1.00)	0.569 (1.00)
PCDH15	22 (19%)	94	0.843 (1.00)	0.863 (1.00)	0.721 (1.00)	0.885 (1.00)	0.71 (1.00)	0.952 (1.00)
SPRYD5	8 (7%)	108	0.341 (1.00)	0.0343 (1.00)	1 (1.00)	0.643 (1.00)	0.307 (1.00)	0.805 (1.00)
TUSC3	9 (8%)	107	0.348 (1.00)	0.88 (1.00)	0.488 (1.00)		1 (1.00)	0.815 (1.00)
FGF22	3 (3%)	113	0.193 (1.00)		1 (1.00)		1 (1.00)	0.324 (1.00)
HLA-B	9 (8%)	107	0.0908 (1.00)	0.00377 (0.939)	0.607 (1.00)	1 (1.00)	0.869 (1.00)	0.666 (1.00)
PTH2	3 (3%)	113	1 (1.00)	0.302 (1.00)			0.143 (1.00)	0.8 (1.00)
C17ORF63	3 (3%)	113	0.193 (1.00)		1 (1.00)		1 (1.00)	1 (1.00)
SMAD4	7 (6%)	109	0.662 (1.00)	0.859 (1.00)	1 (1.00)	0.745 (1.00)	0.85 (1.00)	1 (1.00)
POTEG	6 (5%)	110	0.228 (1.00)	0.48 (1.00)	1 (1.00)	1 (1.00)	0.662 (1.00)	0.36 (1.00)
RNF43	13 (11%)	103	0.000998 (0.251)	0.0168 (1.00)	0.698 (1.00)	0.732 (1.00)	0.184 (1.00)	0.0507 (1.00)
WBSCR17	12 (10%)	104	0.342 (1.00)	0.00419 (1.00)	0.607 (1.00)	0.643 (1.00)	0.241 (1.00)	0.451 (1.00)
PHF2	12 (10%)	104	0.00156 (0.391)	0.0128 (1.00)	0.664 (1.00)	0.0472 (1.00)	0.0414 (1.00)	0.0272 (1.00)
TPTE	14 (12%)	102	0.353 (1.00)	1 (1.00)	0.412 (1.00)	0.84 (1.00)	0.212 (1.00)	0.498 (1.00)
CDH1	11 (9%)	105	0.166 (1.00)	0.769 (1.00)	0.607 (1.00)	0.745 (1.00)	0.0812 (1.00)	0.0936 (1.00)
CPS1	13 (11%)	103	0.648 (1.00)	0.223 (1.00)	1 (1.00)	0.863 (1.00)	0.902 (1.00)	0.132 (1.00)
INO80E	5 (4%)	111	0.349 (1.00)		0.607 (1.00)	0.279 (1.00)	0.348 (1.00)	1 (1.00)
ELF3	5 (4%)	111	0.0424 (1.00)	0.163 (1.00)	1 (1.00)		0.622 (1.00)	0.077 (1.00)
PARK2	9 (8%)	107	0.162 (1.00)	0.0548 (1.00)	1 (1.00)	0.45 (1.00)	0.869 (1.00)	0.28 (1.00)
LARP4B	5 (4%)	111	0.0424 (1.00)	0.174 (1.00)	1 (1.00)		0.622 (1.00)	0.077 (1.00)
OR6K3	6 (5%)	110	0.228 (1.00)	0.358 (1.00)	1 (1.00)	0.387 (1.00)	0.522 (1.00)	0.868 (1.00)
TM7SF4	7 (6%)	109	0.351 (1.00)	0.223 (1.00)	0.488 (1.00)		0.85 (1.00)	0.267 (1.00)
UPF3A	6 (5%)	110	0.228 (1.00)	0.174 (1.00)	0.607 (1.00)	0.745 (1.00)	0.522 (1.00)	0.222 (1.00)
C7ORF63	5 (4%)	111	0.349 (1.00)		1 (1.00)	1 (1.00)	0.622 (1.00)	0.507 (1.00)
KDM4B	10 (9%)	106	0.046 (1.00)	0.0343 (1.00)	0.345 (1.00)	0.45 (1.00)	0.873 (1.00)	0.627 (1.00)
KIAA0748	7 (6%)	109	0.868 (1.00)	0.545 (1.00)	1 (1.00)		0.256 (1.00)	0.599 (1.00)
OR8B4	3 (3%)	113	0.193 (1.00)	0.00894 (1.00)			1 (1.00)	0.604 (1.00)
POM121L12	7 (6%)	109	0.0358 (1.00)	0.122 (1.00)	1 (1.00)	0.745 (1.00)	0.85 (1.00)	0.309 (1.00)
RASA1	9 (8%)	107	0.571 (1.00)	0.551 (1.00)	0.664 (1.00)	0.73 (1.00)	0.175 (1.00)	0.495 (1.00)
SLITRK6	10 (9%)	106	0.0352 (1.00)	0.88 (1.00)	0.108 (1.00)	0.745 (1.00)	0.174 (1.00)	0.835 (1.00)
TP53TG5	4 (3%)	112	0.499 (1.00)		1 (1.00)		1 (1.00)	0.808 (1.00)
LHCGR	7 (6%)	109	1 (1.00)	0.813 (1.00)	0.488 (1.00)		0.709 (1.00)	0.267 (1.00)

'TP53 MUTATION STATUS' versus 'CN_CNMF'

P value = 0.000271 (Fisher's exact test), Q value = 0.07

Table S1. Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	50	50	15
TP53 MUTATED	12	32	7
TP53 WILD-TYPE	38	18	8

Figure S1. Get High-res Image Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #1: 'CN_CNMF'

'TP53 MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 3.69e-05 (Fisher's exact test), Q value = 0.0095

Table S2. Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #6: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	27	56	32
TP53 MUTATED	22	20	9
TP53 WILD-TYPE	5	36	23

Figure S2. Get High-res Image Gene #5: 'TP53 MUTATION STATUS' versus Clinical Feature #6: 'MIRSEQ_CHIERARCHICAL'

'PIK3CA MUTATION STATUS' versus 'METHLYATION_CNMF'

P value = 1.26e-06 (Fisher's exact test), Q value = 0.00033

Table S3. Gene #8: 'PIK3CA MUTATION STATUS' versus Clinical Feature #2: 'METHLYATION_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3	CLUS_4
ALL	9	14	22	23
PIK3CA MUTATED	9	4	3	2
PIK3CA WILD-TYPE	0	10	19	21

Figure S3. Get High-res Image Gene #8: 'PIK3CA MUTATION STATUS' versus Clinical Feature #2: 'METHLYATION_CNMF'

'PIK3CA MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.000704 (Fisher's exact test), Q value = 0.18

Table S4. Gene #8: 'PIK3CA MUTATION STATUS' versus Clinical Feature #6: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	27	56	32
PIK3CA MUTATED	2	20	2
PIK3CA WILD-TYPE	25	36	30

Figure S4. Get High-res Image Gene #8: 'PIK3CA MUTATION STATUS' versus Clinical Feature #6: 'MIRSEQ_CHIERARCHICAL'

'ACVR2A MUTATION STATUS' versus 'CN_CNMF'

P value = 0.000643 (Fisher's exact test), Q value = 0.16

Table S5. Gene #9: 'ACVR2A MUTATION STATUS' versus Clinical Feature #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	50	50	15
ACVR2A MUTATED	11	0	2
ACVR2A WILD-TYPE	39	50	13

Figure S5. Get High-res Image Gene #9: 'ACVR2A MUTATION STATUS' versus Clinical Feature #1: 'CN_CNMF'

'ARID1A MUTATION STATUS' versus 'CN_CNMF'

P value = 0.00027 (Fisher's exact test), Q value = 0.07

Table S6. Gene #11: 'ARID1A MUTATION STATUS' versus Clinical Feature #1: 'CN_CNMF'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	50	50	15
ARID1A MUTATED	18	3	1
ARID1A WILD-TYPE	32	47	14

Figure S6. Get High-res Image Gene #11: 'ARID1A MUTATION STATUS' versus Clinical Feature #1: 'CN_CNMF'

'ARID1A MUTATION STATUS' versus 'MIRSEQ_CHIERARCHICAL'

P value = 0.000467 (Fisher's exact test), Q value = 0.12

Table S7. Gene #11: 'ARID1A MUTATION STATUS' versus Clinical Feature #6: 'MIRSEQ_CHIERARCHICAL'

nPatients	CLUS_1	CLUS_2	CLUS_3
ALL	27	56	32
ARID1A MUTATED	0	18	4
ARID1A WILD-TYPE	27	38	28

Figure S7. Get High-res Image Gene #11: 'ARID1A MUTATION STATUS' versus Clinical Feature #6: 'MIRSEQ_CHIERARCHICAL'

Methods & Data

Input

Mutation data file = STAD-TP.mutsig.cluster.txt
Molecular subtypes file = STAD-TP.transferedmergedcluster.txt
Number of patients = 116
Number of significantly mutated genes = 47
Number of Molecular subtypes = 6
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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