Ovarian Serous Cystadenocarcinoma: Association of mutation, copy number alteration, and subtype markers with pathways
Maintained by Spring Yingchun Liu (Dana-Farber Cancer 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 20 genes with significant mutation (Q value <= 0.1) and 252 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 :

4 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_RACCYCD_PATHWAY | 26 | 5 | 3.9 | 0 | 0.003
BIOCARTA_CHREBP2_PATHWAY | 44 | 6 | 3.4 | 0 | 0.003
KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS | 137 | 9 | 2.4 | 0.0001 | 0.0066
KEGG_OOCYTE_MEIOSIS | 114 | 8 | 2.4 | 0.0001 | 0.0087
KEGG_PANCREATIC_CANCER | 70 | 6 | 2.7 | 0.0003 | 0.019

List of CNV_Mut genes in this pathway

AKT1,CCNE1,RAC1,CHUK,RB1

List of CNV_Mut genes in this pathway

PPP2R5D,PPP2R2D,YWHAE,YWHAQ,PPP2R5E,PPP2R2A

List of CNV_Mut genes in this pathway

BTRC,CUL7,KLHL9,CUL1,ANAPC2,BRCA1,UBE2G2,UBE2M,UBE3C

List of CNV_Mut genes in this pathway

PPP2R5D,BTRC,CUL1,ANAPC2,PPP2R5E,CCNE1,YWHAE,YWHAQ

List of CNV_Mut genes in this pathway

AKT1,CHUK,RB1,KRAS,RAC1,BRCA2

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
--- | --- | --- | --- | --- | ---
KEGG_RIBOSOME | 87 | 19 | 1.3 | 0.0001 | 0.019
KEGG_MAPK_SIGNALING_PATHWAY | 267 | 41 | 0.82 | 0.0001 | 0.019
BIOCARTA_NTHI_PATHWAY | 24 | 8 | 1.9 | 0.0006 | 0.052
BIOCARTA_PML_PATHWAY | 17 | 6 | 2 | 0.0021 | 0.074
BIOCARTA_TEL_PATHWAY | 18 | 6 | 1.9 | 0.0029 | 0.074

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

RPL36AL,RPL14,RPL13,RPS27L,RPL22L1,RPLP1,FAU,RPS18,RPS10,UBA52,RPL35,RPL27A,RPS27,RPL9,RPL10A,RPSA,RPL24,MRPL23,RPL18A

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

MEF2C,PLA2G2E,CACNB2,KRAS,DUSP14,TAOK3,TGFBR2,FGF6,NFKB1,NFKB2,DAXX,MYC,GADD45G,MAP3K14,MAP3K11,SOS1,GPI,RPS6KA4,DUSP1,RPS6KA1,DUSP6,GNA12,FGF11,TGFB1,RELA,STK4,ARRB1,STMN1,TRAF2,ELK1,CACNA2D1,ATF4,AKT2,TNF,PPM1B,TNFRSF1A,RASGRP4,RASGRP1,MAPK8IP2,MAPK8IP3,MAPK8IP1

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

TNF,IL8,RELA,TGFBR2,NFKB1,EP300,DUSP1,MAP3K14

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

TNF,RB1,DAXX,TNFRSF1A,SUMO1,PRAM1

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

XRCC5,RB1,KRAS,TNKS,MYC,TERF1

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
--- | --- | --- | --- | --- | ---
BIOCARTA_GH_PATHWAY | 28 | 6 | 1.3 | 0.028 | 0.74
BIOCARTA_STEM_PATHWAY | 15 | 4 | 1.6 | 0.034 | 0.74
BIOCARTA_LONGEVITY_PATHWAY | 15 | 4 | 1.6 | 0.034 | 0.74
KEGG_PENTOSE_AND_GLUCURONATE_INTERCONVERSIONS | 28 | 6 | 1.3 | 0.024 | 0.74
KEGG_GALACTOSE_METABOLISM | 26 | 6 | 1.4 | 0.02 | 0.74

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

HNF1A,STAT5B,PIK3CA,PRKCA,MAPK1,GH1

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

IL5,CD8A,CSF1,EPO

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

SOD1,SOD2,GH1,PIK3CA

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

UGDH,UGT1A7,UGT1A6,UGT1A10,AKR1B1,UGT2B10

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

HK1,HK3,B4GALT1,PFKM,GANC,AKR1B1

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 | 16 | 1.3 | 0.0004 | 0.11
KEGG_HUNTINGTONS_DISEASE | 183 | 28 | 0.9 | 0.0006 | 0.11
BIOCARTA_MAPK_PATHWAY | 87 | 17 | 1.2 | 0.0011 | 0.12
KEGG_ALZHEIMERS_DISEASE | 167 | 25 | 0.87 | 0.0017 | 0.14
KEGG_COLORECTAL_CANCER | 62 | 13 | 1.2 | 0.0021 | 0.14

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

CTNNB1,MAP3K7,RHOA,EGFR,FARP2,PARD3,ERBB2,ACP1,SORBS1,RAC1,MLLT4,PTPRB,TCF7,GPI,SMAD4,SNAI1

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

COX5A,SIN3A,GRIN2B,RCOR1,PPARGC1A,DCTN2,ATP5C1,APEX1,NFE2L1,ATP5D,UQCRQ,NDUFS6,CASP9,DLG4,NDUFS3,ATP5H,GNAQ,DNAH1,COX7A2L,POLR2D,POLR2C,NDUFB1,NDUFB2,NDUFA3,NDUFA8,NDUFA1,BAX,APAF1

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

MEF2A,MAP3K7,FOS,MAP3K8,MAP4K4,RIPK1,MAPK7,MAP3K13,MAP3K12,MAP3K3,MAP3K2,RAC1,MAPK10,MEF2D,RPS6KA3,RPS6KA4,ARAF

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

COX5A,GRIN2B,ATP5C1,EIF2AK3,ATP2A3,ATP5D,UQCRQ,NDUFS6,CASP9,MAPT,NDUFS3,ATP5H,GNAQ,ERN1,COX7A2L,NDUFB1,NDUFB2,NOS1,NDUFA3,NDUFA8,CAPN2,NDUFA1,NCSTN,LRP1,APAF1

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

CTNNB1,FOS,CASP9,RHOA,AKT3,PIK3CB,KRAS,RAC1,TCF7,SMAD4,MAPK10,BAX,ARAF

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)
Meta

- Maintainer = Spring Yingchun Liu

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