Uterine Corpus Endometrioid Carcinoma: Association of mutation, copy number alteration, and subtype markers with pathways<BR>(primary solid tumor cohort)

Uterine Corpus Endometrioid Carcinoma: Association of mutation, copy number alteration, and subtype markers with pathways
(primary solid tumor cohort)

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 18 genes with significant mutation (Q value <= 0.1) and 330 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 :

2 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	2.8	0	0.0005
BIOCARTA_STRESS_PATHWAY	25	5	3.6	0	0.0081
BIOCARTA_TNFR1_PATHWAY	29	5	3.4	0.0001	0.011
BIOCARTA_ETS_PATHWAY	18	4	3.8	0.0002	0.016
BIOCARTA_HIVNEF_PATHWAY	56	6	2.7	0.0003	0.021

List of CNV_Mut genes in this pathway

RPL14,RPLP2,RPS17,RPL35,RPL7A,RPL4,RPL27,RPS7,MRPL23,RPL18A

List of CNV_Mut genes in this pathway

TRAF2,CASP2,MAP2K3,MAP2K4,TRADD

List of CNV_Mut genes in this pathway

TRAF2,CASP2,MAP2K4,TRADD,PARP1

List of CNV_Mut genes in this pathway

HRAS,RBL2,SIN3B,SIN3A

List of CNV_Mut genes in this pathway

CASP9,CASP2,TRAF2,RASA1,TRADD,PARP1

+ 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