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

Colon 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 119 genes with significant mutation (Q value <= 0.1) and 328 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, 2000 for subtype 4. 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

1 pathways significantly enriched with marker genes of gene expression subtype 3

1 pathways significantly enriched with marker genes of gene expression subtype 4

- 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	3.3	0	0.0092
BIOCARTA_HIVNEF_PATHWAY	56	7	2.6	0.0002	0.029
BIOCARTA_FAS_PATHWAY	30	5	3	0.0004	0.043
BIOCARTA_CERAMIDE_PATHWAY	22	4	3.1	0.0011	0.09
BIOCARTA_G2_PATHWAY	24	4	3	0.0015	0.1

List of CNV_Mut genes in this pathway

PRKDC,BAG4,CASP3,CASP8,MAP2K4,RB1

List of CNV_Mut genes in this pathway

BAG4,CASP3,CASP8,CHUK,RB1,PSEN1,PRKDC

List of CNV_Mut genes in this pathway

PRKDC,CASP3,CASP8,MAP2K4,RB1

List of CNV_Mut genes in this pathway

MAP2K4,RAF1,CASP8,NSMAF

List of CNV_Mut genes in this pathway

PRKDC,ATM,CDC25B,RPS6KA1

+ 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_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION	118	25	1.3	0	0.0038
KEGG_LYSOSOME	121	24	1.2	0.0001	0.0097
KEGG_GAP_JUNCTION	90	17	1.1	0.0014	0.097
KEGG_NOTCH_SIGNALING_PATHWAY	47	11	1.4	0.002	0.1
KEGG_MISMATCH_REPAIR	23	7	1.8	0.0027	0.11

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

MMP9,VCL,RAPGEF4,PIK3CG,PIK3CD,ACTN1,CTNNA2,ITGAL,GNAI3,RAC2,VAV2,PLCG2,RAP1B,CLDN8,PRKCG,TXK,CLDN18,CLDN10,CDH5,VCAM1,EZR,MLLT4,CLDN23,MAPK13,MAPK14

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

AP4M1,ACP5,PPT2,PPT1,SLC11A2,SCARB2,ENTPD4,LAPTM4B,LAMP2,ASAH1,GLB1,CLN3,ATP6V1H,SORT1,CTSC,CTSH,CLN5,TCIRG1,PSAP,AP4S1,MANBA,ARSA,CTNS,GGA3

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

ADCY3,TUBB2A,GUCY1A3,PRKACB,RP11-631M21.2,TUBB1,PLCB1,TUBA1A,PLCB2,TUBA1C,PRKCG,ADRB1,GUCY1B3,GNAI3,MAP3K2,MAP2K1,HTR2B

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

LFNG,PTCRA,KAT2A,KAT2B,DTX3L,DTX2,DLL3,NOTCH1,EP300,PSEN1,RBPJ

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

EXO1,SSBP1,MLH3,POLD3,RPA1,RFC5,RPA2

+ 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_GLYCOSAMINOGLYCAN_BIOSYNTHESIS_HEPARAN_SULFATE	26	8	1.8	0.0012	0.095
KEGG_ENDOCYTOSIS	183	29	0.88	0.0007	0.095
KEGG_HEMATOPOIETIC_CELL_LINEAGE	88	17	1.2	0.0008	0.095
KEGG_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION	118	21	1	0.0009	0.095
BIOCARTA_LAIR_PATHWAY	17	6	2	0.0022	0.14

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

NDST3,HS3ST6,NDST4,NDST2,HS3ST2,HS6ST3,GLCE,HS3ST3B1

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

CHMP5,CHMP4A,VPS4B,DNAJC6,ITCH,PLD1,HLA-A,HLA-E,HLA-G,HLA-F,ACAP1,ARFGAP3,FGFR4,ADRBK1,ARF6,AP2M1,CSF1R,NEDD4,CLTA,ZFYVE20,CXCR4,RAB11FIP4,RAB11FIP2,ADRB2,CHMP1B,HSPA2,EHD1,CBL,RAB31

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

CD8A,GYPA,GP5,CD44,MS4A1,THPO,CD3G,CD3D,CD7,CSF1R,IL7,CD1C,CD1B,ITGA2,CD55,CD19,IL5RA

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

MMP9,RAPGEF4,PIK3CG,ROCK2,NCF4,MYL7,GNAI2,RAC2,VAV3,VAV2,VAV1,PLCG2,CLDN8,CLDN5,CXCR4,ICAM1,CLDN17,CLDN10,CDH5,VCAM1,RASSF5

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

KNG1,C7,ICAM1,IL8,VCAM1,SELPLG

+ 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_DRUG_METABOLISM_CYTOCHROME_P450	72	7	3.2	0	0.0027
KEGG_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450	70	6	3.1	0.0001	0.012
KEGG_GLUTATHIONE_METABOLISM	50	4	3	0.0016	0.17
KEGG_O_GLYCAN_BIOSYNTHESIS	30	3	3.3	0.0035	0.29
KEGG_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION	118	5	2	0.0068	0.45

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

ADH1C,ADH1A,CYP2A6,GSTA2,GSTA3,GSTA5,MGST1

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

ADH1C,ADH1A,GSTA2,GSTA3,GSTA5,MGST1

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

GSTA2,GSTA3,GSTA5,MGST1

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

GALNT4,GALNTL2,ST6GALNAC1

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

CLDN2,CLDN15,NOX1,MAPK12,MAPK14

+ The top five pathways enriched with marker genes of gene expression subtype 4

Table 5. Get Full Table Top Pathways enriched with marker genes of gene expression subtype 4 . Nof Genes : No. of genes in this pathway. Nof Marker : No. of marker genes of gene expression subtype 4 in this pathway. Enrichment , P value and Q value : See Methods & Data below. Marker Gene in Pathway: markers of gene expression subtype 4 in this pathway

Pathway	Nof Genes	Nof Marker	Enrichment	P value	Q value
KEGG_AXON_GUIDANCE	129	25	1.5	0	0.0006
KEGG_TGF_BETA_SIGNALING_PATHWAY	86	14	1.2	0.002	0.34
BIOCARTA_TEL_PATHWAY	18	5	2	0.0064	0.36
KEGG_PHENYLALANINE_METABOLISM	18	5	2	0.0064	0.36
KEGG_LYSOSOME	121	16	0.91	0.0087	0.36