Uterine Corpus Endometrioid Carcinoma: 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 61 genes with significant mutation (Q value <= 0.1) and 340 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 921 for subtype 1, 921 for subtype 2, 921 for subtype 3. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

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

2 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
--- | --- | --- | --- | --- | ---
KEGG_RIBOSOME | 87 | 10 | 2.6 | 0 | 0.0017
BIOCARTA_DEATH_PATHWAY | 33 | 5 | 3 | 0.0004 | 0.024
BIOCARTA_ETS_PATHWAY | 18 | 4 | 3.6 | 0.0003 | 0.024
BIOCARTA_TNFR1_PATHWAY | 29 | 5 | 3.2 | 0.0002 | 0.024
KEGG_SPLICEOSOME | 126 | 9 | 2.1 | 0.0003 | 0.024

List of CNV_Mut genes in this pathway

RPL14,RPLP2,UBA52,RPL35,RPL7A,RPS21,RPL27,RPS7,MRPL23,RPL18A

List of CNV_Mut genes in this pathway

TRAF2,CASP9,TRADD,TNFRSF10A,TNFRSF10B

List of CNV_Mut genes in this pathway

HRAS,RBL2,SIN3B,SIN3A

List of CNV_Mut genes in this pathway

TRAF2,CASP2,MAP2K4,TRADD,PARP1

List of CNV_Mut genes in this pathway

CHERP,LSM4,SF3B14,EFTUD2,AQR,RBMX,PRPF8,TXNL4A,RBM17

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_CELL_CYCLE | 128 | 22 | 2.2 | 0 | 0
KEGG_DNA_REPLICATION | 36 | 8 | 2.5 | 0.0001 | 0.0097
KEGG_OOCYTE_MEIOSIS | 114 | 14 | 1.7 | 0.0001 | 0.013
BIOCARTA_CELLCYCLE_PATHWAY | 23 | 6 | 2.7 | 0.0002 | 0.016
BIOCARTA_MCM_PATHWAY | 18 | 5 | 2.8 | 0.0005 | 0.024

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

DBF4,TTK,PTTG2,PTTG1,CCNA2,RBL1,ANAPC4,SKP2,CHEK1,CDC20,PLK1,E2F1,CCNE1,CCNH,MCM2,MCM4,CDK2,MCM6,GADD45A,BUB1,CCNB1,CCNB2

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

FEN1,MCM2,RNASEH2A,MCM4,MCM6,RFC3,RFC4,RFC2

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

PTTG2,AURKA,PTTG1,PGR,SGOL1,ANAPC4,CDC20,PLK1,CCNE1,CDK2,CALML3,BUB1,CCNB1,CCNB2

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

E2F1,CCNH,RBL1,CDK2,CCNB1,CCNE1

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

MCM2,MCM4,CDK2,MCM6,CCNE1

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_NO2IL12_PATHWAY | 17 | 2 | 4.3 | 0.0047 | 0.39
BIOCARTA_TOB1_PATHWAY | 21 | 2 | 4.1 | 0.0059 | 0.39
BIOCARTA_CTLA4_PATHWAY | 21 | 2 | 4.2 | 0.0053 | 0.39
KEGG_PATHOGENIC_ESCHERICHIA_COLI_INFECTION | 59 | 3 | 3.2 | 0.0044 | 0.39
WNT_SIGNALING | 89 | 4 | 2.9 | 0.0022 | 0.39

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

CD3D,CXCR3

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

CD3D,TOB1

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

CD3D,CTLA4

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

TUBB2B,ARPC5,ACTB

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

WNT4,ACTB,FZD7,KREMEN1

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_OOCYTE_MEIOSIS | 114 | 12 | 1.9 | 0.0001 | 0.025
KEGG_CELL_CYCLE | 128 | 11 | 1.6 | 0.0008 | 0.13
BIOCARTA_MYOSIN_PATHWAY | 31 | 5 | 2.5 | 0.0016 | 0.18
BIOCARTA_CSK_PATHWAY | 24 | 4 | 2.7 | 0.003 | 0.24
KEGG_GRAFT_VERSUS_HOST_DISEASE | 42 | 5 | 2.3 | 0.0036 | 0.24

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

PTTG2,AURKA,PTTG1,PGR,ANAPC4,CDC20,CCNE1,CALML3,BUB1,CALML6,CDC25C,ADCY9

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

PTTG2,PTTG1,CDKN2A,ANAPC4,CDC20,CCNE1,MDM2,GADD45B,BUB1,CDC25C,CDC25A

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

PLCB1,ARHGEF3,ARHGEF7,ARHGEF17,PKN1

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

PTPRC,CD3D,ZAP70,HLA-DRA

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

HLA-DRB5,HLA-DPB1,HLA-DPA1,KLRC1,HLA-DRA

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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