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.

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)
Copyright © 2011 Broad Institute TCGA GDAC as part of the TCGA Research Network. All rights reserved.
Made with Nozzle