Colon/Rectal Adenocarcinoma: 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 439 genes with significant mutation (Q value <= 0.1) and 371 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_TNFR1_PATHWAY | 29 | 6 | 2.4 | 0.0007 | 0.078
KEGG_APOPTOSIS | 88 | 11 | 1.7 | 0.0005 | 0.078
KEGG_PROSTATE_CANCER | 89 | 11 | 1.7 | 0.0006 | 0.078
KEGG_ERBB_SIGNALING_PATHWAY | 87 | 10 | 1.6 | 0.0019 | 0.098
KEGG_ADHERENS_JUNCTION | 75 | 9 | 1.7 | 0.0019 | 0.098

List of CNV_Mut genes in this pathway

PRKDC,BAG4,CASP3,CASP8,MAP2K4,RB1

List of CNV_Mut genes in this pathway

CASP3,CASP8,CHUK,TNFRSF10A,TNFRSF10C,TNFRSF10B,TNFRSF10D,BCL2L1,PPP3CC,PIK3R1,IKBKB

List of CNV_Mut genes in this pathway

PTEN,CTNNB1,CHUK,RB1,PDGFRA,FGFR1,ERBB2,PIK3R1,MAP2K2,GSK3B,IKBKB

List of CNV_Mut genes in this pathway

EIF4EBP1,NRG1,ERBB4,ERBB3,ERBB2,PIK3R1,MAP2K2,MAP2K4,MAPK10,GSK3B

List of CNV_Mut genes in this pathway

IQGAP1,CTNNB1,RHOA,PTPRM,CTNNA1,FGFR1,ERBB2,TGFBR2,SMAD3

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_HEMATOPOIETIC_CELL_LINEAGE | 88 | 17 | 1.2 | 0.0007 | 0.23
KEGG_PRIMARY_BILE_ACID_BIOSYNTHESIS | 16 | 6 | 2.1 | 0.0015 | 0.24
BIOCARTA_CTLA4_PATHWAY | 21 | 6 | 1.9 | 0.003 | 0.25
KEGG_LYSOSOME | 121 | 20 | 0.92 | 0.0031 | 0.25
BIOCARTA_TALL1_PATHWAY | 15 | 5 | 1.9 | 0.0068 | 0.31

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

CD8A,GYPA,CD3D,CD38,CD37,TNF,ITGB3,CD9,FCGR1A,IL2RA,IL7,FLT3,ITGA4,CD19,ITGA6,EPOR,CD14

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

AMACR,CYP39A1,CYP27A1,CH25H,HSD17B4,AKR1D1

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

CD3D,CD247,CTLA4,PTPN11,CD80,CD28

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

GNPTG,NEU1,NAGLU,ACP5,CTSA,PPT1,LAPTM5,ABCB9,LAMP2,AP1S3,AP1S2,ATP6V0D2,HYAL1,CTSS,DNASE2B,CTSK,PSAPL1,CEL,MANBA,SLC17A5

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

TRAF2,TNFRSF17,TNFSF13B,MAPK8,MAP3K14

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_IL12_PATHWAY | 23 | 8 | 2.1 | 0.0003 | 0.048
BIOCARTA_NO2IL12_PATHWAY | 17 | 7 | 2.2 | 0.0003 | 0.048
BIOCARTA_TOB1_PATHWAY | 21 | 7 | 2.1 | 0.001 | 0.1
KEGG_STEROID_BIOSYNTHESIS | 17 | 6 | 2.1 | 0.0016 | 0.12
BIOCARTA_CTLA4_PATHWAY | 21 | 6 | 1.9 | 0.0042 | 0.25

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

IL18R1,CD3G,CD3D,CD3E,TRA@,IL12RB2,IL12RB1,IL12A

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

CD3G,CD3D,CD3E,IL12RB2,IL12RB1,IL12A,CD4

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

CD3G,CD3D,CD3E,TGFBR2,SMAD4,TRA@,TOB1

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

SOAT1,CEL,CYP27B1,SQLE,DHCR7,NSDHL

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

CD3G,CD3D,CD3E,CTLA4,TRA@,PIK3R1

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_PURINE_METABOLISM | 158 | 29 | 1 | 0.0001 | 0.032
KEGG_MATURITY_ONSET_DIABETES_OF_THE_YOUNG | 25 | 8 | 1.8 | 0.0009 | 0.15
BIOCARTA_MCM_PATHWAY | 18 | 5 | 1.6 | 0.016 | 0.49
BIOCARTA_CELLCYCLE_PATHWAY | 23 | 6 | 1.6 | 0.012 | 0.49
KEGG_STEROID_BIOSYNTHESIS | 17 | 5 | 1.8 | 0.0097 | 0.49

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

ADCY5,POLE,PDE4D,POLR2J2,NME7,PDE5A,PPAT,PDE6B,ENTPD5,ADSSL1,AK7,PDE6H,POLD3,PDE7B,GUK1,PDE11A,NT5M,PDE8A,NT5E,POLR1E,PDE10A,GMPR,ADK,POLR2H,POLR2I,POLR2C,PDE1C,NUDT9,POLR3A

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

ONECUT1,PAX4,BHLHA15,NKX2-2,HNF4G,NEUROG3,MNX1,KLRG1

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

MCM4,CDK2,CCNE1,ORC3L,CDKN1B

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

E2F1,CDK7,CDC25A,CDK2,CCNE1,CDKN1B

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

TM7SF2,SOAT1,GLB1,CEL,CYP27B1

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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