Rectum Adenocarcinoma: Association of mutation, copy number alteration, and subtype markers with pathways<BR>(primary solid tumor cohort)

Rectum Adenocarcinoma: 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 20 genes with significant mutation (Q value <= 0.1) and 508 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 1088 for subtype 1, 1088 for subtype 2, 1088 for subtype 3. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

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

0 pathways significantly enriched with marker genes of gene expression subtype 1

1 pathways significantly enriched with marker genes of gene expression subtype 2

15 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_PARKINSONS_DISEASE	130	13	2.2	0	0.0013
BIOCARTA_CHREBP2_PATHWAY	44	7	2.7	0.0001	0.0068
KEGG_RNA_DEGRADATION	55	8	2.5	0.0001	0.0068
KEGG_NEUROTROPHIN_SIGNALING_PATHWAY	126	12	1.9	0.0001	0.0068
KEGG_SPLICEOSOME	126	11	2	0.0001	0.0088

List of CNV_Mut genes in this pathway

COX5A,VDAC2,VDAC3,ATP5E,UBE2G1,CASP9,NDUFS2,ATP5H,UBB,NDUFB8,ATP5F1,PARK7,SDHD

List of CNV_Mut genes in this pathway

PPP2R5D,PPP2CB,PPP2R2D,YWHAB,YWHAE,PPP2R5E,PPP2R2A

List of CNV_Mut genes in this pathway

LSM7,CNOT2,CNOT7,LSM1,EXOSC1,XRN2,WDR61,DCP1B

List of CNV_Mut genes in this pathway

PIK3CA,RIPK2,MAPK7,KRAS,RAP1A,IKBKB,CDC42,CAMK2G,YWHAB,YWHAE,NRAS,CALM1

List of CNV_Mut genes in this pathway

LSM7,CTNNBL1,HNRNPC,SNRPB2,SNW1,CRNKL1,MAGOHB,CDC5L,WBP11,PRPF8,BCAS2

+ 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_ECM_RECEPTOR_INTERACTION	84	14	1.8	0	0.014
KEGG_FOCAL_ADHESION	201	21	1.1	0.0006	0.095
KEGG_CELL_ADHESION_MOLECULES_CAMS	134	15	1.2	0.0014	0.15
KEGG_TIGHT_JUNCTION	134	14	1.1	0.004	0.24
KEGG_PATHWAYS_IN_CANCER	328	27	0.77	0.0039	0.24

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

SV2B,SV2A,COL11A1,COL1A2,LAMC1,ITGA11,ITGB3,COMP,ITGB7,ITGB6,THBS2,THBS4,COL4A4,HSPG2

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

CTNNB1,PPP1CA,LAMC1,ITGA11,RAC1,KDR,COL11A1,THBS2,THBS4,PDGFC,COL1A2,ITGB3,DOCK1,ITGB7,ITGB6,MYLK,AKT3,SHC4,VASP,COMP,COL4A4

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

NCAM1,PHOX2A,CD226,ITGB7,HLA-DOA,CLDN6,NRXN1,SIGLEC1,CD80,CNTN1,CLDN2,CLDN19,CDH5,NLGN2,NLGN3

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

AMOTL1,CTNNB1,MPDZ,MYH4,MYH7B,PPP2R2B,PARD6B,MYH13,MYH10,CLDN6,AKT3,EPB41L1,CLDN2,CLDN19

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

SHH,CTNNB1,CUL2,RARB,LAMC1,RAC1,FGF5,MITF,SPI1,GLI2,GLI3,GLI1,NOS2,AKR1B1,FZD8,FOXO1,FGF12,WNT4,RALA,FGFR1,AKT3,RUNX1T1,CDK2,NCOA4,TCF7L1,COL4A4,KLK3

+ 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_VIRAL_MYOCARDITIS	73	13	2	0	0.0045
KEGG_FOCAL_ADHESION	201	23	1.3	0.0001	0.013
KEGG_ECM_RECEPTOR_INTERACTION	84	13	1.7	0.0002	0.013
KEGG_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION	118	16	1.5	0.0001	0.013
BIOCARTA_EIF_PATHWAY	16	5	2.8	0.0005	0.02

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

HLA-DMB,HLA-DMA,ACTG1,CASP8,MYH4,EIF4G2,CD86,SGCD,HLA-DPA1,MYH7B,SGCA,ITGB2,MYH13

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

ACTG1,ROCK2,ITGA11,SPP1,LAMA1,PTEN,COL11A1,PARVG,COL6A2,THBS2,IGF1,PDGFC,MYL9,ITGAV,ITGA4,MYLK,AKT3,SHC4,PRKCB,TNC,COMP,COL4A4,BAD

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

SDC2,SV2B,COL11A1,TNC,ITGA11,COMP,ITGAV,COL6A2,THBS2,SPP1,COL4A4,ITGA4,LAMA1

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

MMP9,MMP2,ACTG1,NCF2,NCF1,ROCK2,CTNNA1,THY1,ITGB2,MYL9,ITGA4,MSN,PRKCB,VCAM1,MLLT4,CYBB

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

EIF6,EEF2,EIF4G2,EIF4A1,EEF2K

+ 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
BIOCARTA_CTL_PATHWAY	15	8	4
BIOCARTA_CTLA4_PATHWAY	21	8	3.5
KEGG_CYTOKINE_CYTOKINE_RECEPTOR_INTERACTION	267	30	1.6
KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION	89	16	2.4
KEGG_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY	137	22	2.1