Association of mutation, copy number alteration, and subtype markers with pathways

Ovarian Serous Cystadenocarcinoma (Primary solid tumor)

15 January 2014 | analyses__2014_01_15

Maintainer Information

Citation Information

Maintained by Spring Yingchun Liu (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2014): Association of mutation, copy number alteration, and subtype markers with pathways. Broad Institute of MIT and Harvard. doi:10.7908/C1S46QDX

- Overview

+ Introduction

This pipeline maps genes, with mutation or copy number alteration AND this alteration is highly correlated with mRNA expression, to pathways curated in the KEGG and BIOCARTA databases. It identifies pathways significantly enriched with these genes. The pipeline also identifies pathways significantly enriched with marker genes of each expression subtype of cancer.

genes with mutation: identified by the Mutation_Significance pipeline

genes with copy number alteration: identified by the CopyNumber_Gistic2 pipeline

correlation between copy number and mRNA expression: identified by the Correlate_CopyNumber_vs_mRNA pipeline

marker genes and expression subtypes: identified by the mRNAConsensusClustering pipeline

- Summary

There are 2 genes with significant mutation (Q value <= 0.1) and 231 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 2000 for subtype 1, 2000 for subtype 2, 2000 for subtype 3. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

0 pathways significantly enriched with genes with copy number alteration or mutation.

0 pathways significantly enriched with marker genes of gene expression subtype 1

0 pathways significantly enriched with marker genes of gene expression subtype 2

0 pathways significantly enriched with marker genes of gene expression subtype 3

- Results

+ The top five pathways enriched with genes with copy number alteration or mutation

Table 1. Get Full Table Top Pathways enriched with genes with copy number alteration or mutation. Nof Genes : No. of genes in this pathway. Nof CNV_Mut : No. of genes with copy number alteration or mutation in this pathway. Enrichment , P value and Q value : See Methods & Data below. CNV_Mut Genes in Pathway: genes with copy number alteration or mutation in this pathway.

Pathway	Nof Genes	Nof CNV_Mut	Enrichment	P value	Q value
BIOCARTA_TEL_PATHWAY	18	4	4.3	0	0.013
BIOCARTA_MTOR_PATHWAY	23	4	4	0.0001	0.018
BIOCARTA_RACCYCD_PATHWAY	26	4	3.8	0.0002	0.02
KEGG_OOCYTE_MEIOSIS	114	7	2.5	0.0003	0.021
KEGG_SMALL_CELL_LUNG_CANCER	84	6	2.7	0.0003	0.023

List of CNV_Mut genes in this pathway

TP53,AKT1,KRAS,PTEN

List of CNV_Mut genes in this pathway

FKBP1A,PTEN,AKT1,TSC1

List of CNV_Mut genes in this pathway

AKT1,CCNE1,RAC1,CHUK

List of CNV_Mut genes in this pathway

BTRC,CUL1,ANAPC2,PPP2R5E,CCNE1,YWHAQ,CALM3

List of CNV_Mut genes in this pathway

PTEN,AKT1,CCNE1,MAX,CHUK,TP53

+ The top five pathways enriched with marker genes of gene expression subtype 1

Table 2. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 1 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 1 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 1 in this pathway

Pathway	Nof Genes	Nof Marker	Enrichment	P value	Q value
BIOCARTA_AMI_PATHWAY	20	6	1.8	0.0047	0.52
BIOCARTA_INTRINSIC_PATHWAY	23	7	1.8	0.0021	0.52
KEGG_COMPLEMENT_AND_COAGULATION_CASCADES	69	13	1.1	0.0043	0.52
KEGG_RIBOSOME	87	14	0.91	0.012	0.97
BIOCARTA_RELA_PATHWAY	16	0	0	1	1

List of marker genes for gene expression subtype 1 in this pathway

F7,PROC,FGG,FGA,F2,SERPINC1

List of marker genes for gene expression subtype 1 in this pathway

F11,KNG1,PROC,FGG,FGA,F2,SERPINC1

List of marker genes for gene expression subtype 1 in this pathway

CD46,CFD,KNG1,F11,F7,PROC,SERPINF2,F2,MBL2,FGG,FGA,SERPINC1,VWF

List of marker genes for gene expression subtype 1 in this pathway

RPL14,RPS27A,RPS16,RPS17,RPL3L,RPL27A,RPL30,RPS28,RPL6,RPL5,RPL26,RPL23A,RPS7,RPL29

List of marker genes for gene expression subtype 1 in this pathway

+ The top five pathways enriched with marker genes of gene expression subtype 2

Table 3. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 2 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 2 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 2 in this pathway

Pathway	Nof Genes	Nof Marker	Enrichment	P value	Q value
KEGG_ADHERENS_JUNCTION	75	17	1.4	0.0001	0.037
KEGG_RIBOFLAVIN_METABOLISM	16	6	2.1	0.0015	0.17
KEGG_ALZHEIMERS_DISEASE	167	25	0.89	0.0015	0.17
BIOCARTA_MAPK_PATHWAY	87	16	1.1	0.0027	0.22
BIOCARTA_CARM_ER_PATHWAY	35	8	1.4	0.0068	0.32

List of marker genes for gene expression subtype 2 in this pathway

WASF3,VCL,CTNNB1,CTNNA3,PARD3,ERBB2,CDH1,ACP1,TCF7L2,PVRL1,SORBS1,RAC1,YES1,MLLT4,PTPRB,GPI,SNAI1

List of marker genes for gene expression subtype 2 in this pathway

ENPP3,ACP1,ACPP,MTMR2,MTMR6,PHPT1

List of marker genes for gene expression subtype 2 in this pathway

COX5A,EIF2AK3,NDUFA4L2,ATP2A3,NDUFV1,CACNA1D,ATP5D,UQCRQ,NDUFS6,CASP9,ADAM10,ERN1,NDUFB9,PPP3R1,ATP5G2,NDUFB1,NDUFB2,NOS1,NDUFA3,NDUFA8,CAPN2,NDUFA1,SDHA,LRP1,SDHD

List of marker genes for gene expression subtype 2 in this pathway

MEF2A,TGFB2,MAX,MAP3K8,MAP4K3,MAPK4,RIPK1,MAP3K13,MAP3K12,MAP3K3,MAP3K2,RAC1,MAP2K4,RPS6KA3,RPS6KA4,MAPK13

List of marker genes for gene expression subtype 2 in this pathway

TBP,GTF2A1,NR0B1,HIST2H3C,HDAC4,PHB2,CARM1,HDAC6

+ The top five pathways enriched with marker genes of gene expression subtype 3

Table 4. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 3 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 3 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 3 in this pathway

Pathway	Nof Genes	Nof Marker	Enrichment	P value	Q value
KEGG_MATURITY_ONSET_DIABETES_OF_THE_YOUNG	25	9	2	0.0001	0.029
KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION	272	40	0.77	0.0003	0.04
KEGG_GLYCEROLIPID_METABOLISM	49	12	1.5	0.0006	0.047
BIOCARTA_CERAMIDE_PATHWAY	22	7	1.9	0.0017	0.093
KEGG_PRION_DISEASES	35	9	1.6	0.002	0.093