Ovarian Serous Cystadenocarcinoma: Association of mutation, copy number alteration, and subtype markers with pathways
Maintained by Spring Yingchun Liu (Broad Institute)
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 8 genes with significant mutation (Q value <= 0.1) and 258 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_FAS_PATHWAY | 30 | 4 | 3.4 | 0.0005 | 0.054
BIOCARTA_CHREBP2_PATHWAY | 44 | 5 | 3.2 | 0.0002 | 0.054
BIOCARTA_TNFR1_PATHWAY | 29 | 4 | 3.4 | 0.0005 | 0.054
KEGG_RNA_DEGRADATION | 55 | 5 | 2.8 | 0.0006 | 0.054
KEGG_PROSTATE_CANCER | 89 | 6 | 2.4 | 0.0009 | 0.062

List of CNV_Mut genes in this pathway

DFFA,DFFB,MAP2K4,RB1

List of CNV_Mut genes in this pathway

PPP2R5D,PRKAG2,PPP2R2D,PPP2R5E,PPP2R2A

List of CNV_Mut genes in this pathway

DFFA,DFFB,MAP2K4,RB1

List of CNV_Mut genes in this pathway

CNOT2,EXOSC2,EXOSC10,DCP1B,DCP1A

List of CNV_Mut genes in this pathway

PTEN,CASP9,RB1,KRAS,MTOR,IKBKB

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_KERATINOCYTE_PATHWAY | 46 | 12 | 1.6 | 0.0004 | 0.022
BIOCARTA_41BB_PATHWAY | 17 | 7 | 2.2 | 0.0003 | 0.022
KEGG_T_CELL_RECEPTOR_SIGNALING_PATHWAY | 108 | 21 | 1.2 | 0.0003 | 0.022
KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY | 67 | 16 | 1.4 | 0.0001 | 0.022
KEGG_SMALL_CELL_LUNG_CANCER | 84 | 17 | 1.2 | 0.0007 | 0.032

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

TRAF2,TNF,NFKB1,DAXX,TNFRSF1A,CHUK,CEBPA,RELA,MAP2K4,PRKCE,PRKCD,JUN

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

IL4,TRAF2,RELA,NFKB1,MAP4K5,JUN,CHUK

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

RELA,JUN,KRAS,VAV3,NFKB1,PDCD1,PAK6,PAK4,RHOA,AKT3,CHUK,DLG1,TNF,RASGRP1,NFAT5,PIK3R1,CD28,NFATC1,IL4,IL5,FYN

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

NFKB1,SLC2A1,CHUK,AKT3,RELA,PRKAB2,RXRG,ADIPOR2,CD36,TRAF2,TNF,G6PC2,TNFRSF1A,ACSL3,ACACB,NPY

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

E2F2,NFKB1,CCNE1,CDKN2B,MYC,CHUK,AKT3,RELA,CYCS,RXRG,CDK2,PIAS3,TRAF2,LAMB2,PIK3R1,ITGA3,LAMA5

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_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION | 272 | 41 | 0.81 | 0.0001 | 0.047
KEGG_TYROSINE_METABOLISM | 42 | 9 | 1.3 | 0.007 | 0.92
KEGG_PHENYLALANINE_METABOLISM | 18 | 5 | 1.7 | 0.014 | 0.92
KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY | 79 | 13 | 0.94 | 0.012 | 0.92
KEGG_VIBRIO_CHOLERAE_INFECTION | 56 | 10 | 1.1 | 0.013 | 0.92

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

GRIN3B,LTB4R,GRIN2C,CHRNA4,CHRNA2,SSTR4,CRHR2,HTR6,CHRNB2,CHRND,CHRNE,CHRNG,NMUR1,GRM3,GRM2,NPY2R,NPFFR2,MAS1,NPFFR1,OPRL1,PLG,P2RY10,HTR2C,F2RL2,GRIK5,SCTR,GALR3,GALR2,NTSR1,NTSR2,CYSLTR1,DRD4,GABRE,GRIN1,P2RX2,LTB4R2,ADRA1B,LEPR,CHRM5,MLNR,CHRNA10

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

ADH1C,ADH6,COMT,THPO,DDC,HYAL1,MAOB,METTL2B,AOX1

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

DDC,HYAL1,MAOB,PAH,PRDX6

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

PIK3CA,MS4A1,SYK,PRKCE,MAPK1,PLA2G3,RAC3,SOS2,PIK3R5,FCER1A,VAV3,IL5,PLCG2

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

ATP6AP1,KCNQ1,KDELR1,ATP6V1C2,ATP6V1A,ATP6V1G2,SLC12A2,TJP1,PLCG2,ATP6V0A1

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_ADHERENS_JUNCTION | 75 | 17 | 1.4 | 0.0001 | 0.039
KEGG_PENTOSE_PHOSPHATE_PATHWAY | 27 | 8 | 1.8 | 0.0015 | 0.24
KEGG_GLYCINE_SERINE_AND_THREONINE_METABOLISM | 31 | 8 | 1.6 | 0.0038 | 0.31
KEGG_FOCAL_ADHESION | 201 | 29 | 0.73 | 0.0034 | 0.31
BIOCARTA_MAPK_PATHWAY | 87 | 15 | 0.97 | 0.0069 | 0.35

List of marker genes for gene expression subtype 3 in this pathway

CTNNB1,MAP3K7,RHOA,EGFR,ACTN1,FARP2,PARD3,ERBB2,ACP1,TCF7L2,PVRL1,SORBS1,RAC1,MLLT4,PTPRB,GPI,SNAI1

List of marker genes for gene expression subtype 3 in this pathway

ALDOA,TALDO1,RPIA,DDR2,KHSRP,PGM2,GPI,H6PD

List of marker genes for gene expression subtype 3 in this pathway

PSPH,SHMT2,GATM,MAOA,MAOB,PHGDH,PSAT1,CBS

List of marker genes for gene expression subtype 3 in this pathway

CTNNB1,ROCK2,LAMC2,ERBB2,RAC1,MAP2K1,LAMA5,FLNA,CCND2,PARVB,MAPK10,CAPN2,PDGFB,PDGFD,EGFR,ACTN1,PPP1CC,CAV1,ITGB4,MYL9,ITGA8,RHOA,ZYX,SHC3,AKT3,VASP,COMP,PIK3R2,COL4A1

List of marker genes for gene expression subtype 3 in this pathway

MEF2A,TGFB2,MAP3K7,FOS,MAP3K8,MAP4K4,MAPK4,RIPK1,MAP3K12,TRAF2,RAC1,MAP2K1,MAPK10,RPS6KA3,RPS6KA4

Methods & Data
Enrichment

Let genes with copy number alteration or mutation be query genes. Let marker genes of specific identified subtypes be query genes. The Enrichment is calculated as:

- Enrichment = log2 (# of query genes in the pathway/# No of query genes) - log2 (# of genes in the pathway/# of human genes)

P value

The statistical signficance of the pathways that are enriched with genes with copy number alteration or mutation, and the pathways that are enriched with markers genes of specific identified subtypes is measured by P value.

- P value = Fisher exact P value

Q value

The Q value is for adjusting P value for multiple testing. A public available R package is used to calculate the Q value.

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.

- Analysis Results (MD5 checksum)

- Auxiliary Data (MD5 checksum)

- MAGE-TAB File (MD5 checksum)

References
[1] Qi Zheng, GOEAST: a web-based software toolkit for Gene Ontology enrichment analysis, Nucleic Acids Res. 36(issue suppl 2):W358-W363 (2008)
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