Breast Invasive Carcinoma: 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 56 genes with significant mutation (Q value <= 0.1) and 242 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

2 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_CHREBP2_PATHWAY	44	5	3.1	0.0003	0.052
KEGG_PROTEIN_EXPORT	24	4	3.6	0.0003	0.052
BIOCARTA_RACCYCD_PATHWAY	26	4	3.4	0.0005	0.052
BIOCARTA_TNFR1_PATHWAY	29	4	3.3	0.0007	0.06
BIOCARTA_DEATH_PATHWAY	33	4	3.1	0.0012	0.078

List of CNV_Mut genes in this pathway

PPP2CB,PPP2R2D,YWHAE,YWHAQ,PPP2R2A

List of CNV_Mut genes in this pathway

SRP54,SEC63,SRPR,SPCS1

List of CNV_Mut genes in this pathway

TFDP1,RB1,CDKN1B,IKBKB

List of CNV_Mut genes in this pathway

MAP3K7,MAP2K4,RB1,RIPK1

List of CNV_Mut genes in this pathway

BID,TNFRSF10A,TNFRSF10B,RIPK1

+ 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_HUNTINGTONS_DISEASE	183	30	1	0.0001	0.034
KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION	272	38	0.69	0.0015	0.17
KEGG_VIRAL_MYOCARDITIS	73	14	1.3	0.0013	0.17
KEGG_PARKINSONS_DISEASE	130	19	0.98	0.0023	0.19
BIOCARTA_MCALPAIN_PATHWAY	25	6	1.5	0.016	0.3

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

NDUFAB1,TBP,COX5B,BDNF,CREB3L3,DCTN1,COX6B1,AP2M1,NDUFV3,NFE2L1,CLTCL1,CLTA,ATP5B,PPARG,UQCRFS1,NDUFS7,GPX1,CASP3,ATP5H,NDUFS1,UQCRB,POLR2E,POLR2C,NDUFB1,NDUFA3,CREB3,IFT57,SDHD,APAF1,ATP5A1

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

ADORA3,LPAR4,HTR1B,AGTR2,S1PR1,LTB4R,GRID1,CRHR1,CRHR2,SSTR3,SSTR1,GPR156,GH2,CHRNB4,CHRNB2,CHRNB1,CHRNE,NMUR1,RXFP2,GRM2,GRM7,GRM6,GIPR,NPY2R,GALR2,DRD3,ADORA2A,GABRQ,GABRD,GABRA2,P2RX3,CALCRL,PTGER2,PTGER4,CHRM5,PTAFR,OXTR,DHX8

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

MYH15,CASP3,MYH1,HLA-A,EIF4G3,SGCG,CD40LG,CAV1,DAG1,ITGB2,RAC3,CD28,MYH11,ABL2

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

NDUFAB1,COX5B,COX6B1,UBE2L3,NDUFV3,ATP5B,UBE2G2,UQCRFS1,NDUFS7,CASP3,ATP5H,NDUFS1,UQCRB,NDUFB1,NDUFA3,SDHD,ATP5A1,APAF1,SLC18A1

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

CXCR3,ITGB1,PRKACG,PRKAR2B,PTK2,EZR

+ 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_HUNTINGTONS_DISEASE	183	31	1	0.0001	0.016
BIOCARTA_MAPK_PATHWAY	87	17	1.2	0.0011	0.058
KEGG_RIBOSOME	87	17	1.2	0.0009	0.058
KEGG_MAPK_SIGNALING_PATHWAY	267	39	0.74	0.0007	0.058
KEGG_PARKINSONS_DISEASE	130	20	1	0.0011	0.058

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

TBP,CREB3L2,TBPL1,DCTN4,APEX1,AP2M1,GRIN1,VDAC3,DNAL1,AP2S1,ATP5B,CLTC,UQCRFS1,NDUFS7,NDUFS4,NDUFB10,NDUFB3,NDUFB4,POLR2G,NDUFB6,POLR2B,NDUFB2,DNAI1,NDUFA4,NDUFA8,CREB1,NDUFA7,ATP5F1,NDUFA1,SDHC,IFT57

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

MAP3K7,MAP3K5,PAK2,MYC,MAPK8,MAP3K14,MAP3K12,GRB2,MKNK2,MAPKAPK3,MAP3K3,TGFBR1,MAP2K3,CREB1,RPS6KA5,RPS6KA3,MAPK12

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

RPL36AL,RPL19,RPL14,RPL13,RPS3,RPL10,RPS13,UBA52,RPL27A,RPS27,RPL30,RPL32,RPL8,RPS21,RPL23A,RPL13A,RPL21

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

PRKX,MAP3K7,MAP3K5,MAPKSP1,MAPK8,PLA2G2E,CACNB3,TAOK1,MAP2K3,TGFBR1,FGF5,MYC,FGF4,CACNG6,CACNG1,MAP3K14,MAP3K12,MKNK2,RPS6KA5,RPS6KA3,MAPK12,ZAK,STK3,RASGRF1,FGFR4,GRB2,MAPKAPK3,CACNA1S,CACNA2D4,IKBKG,PAK2,AKT2,TNF,MAP3K3,RASGRP4,RASGRP1,NF1,MAPK8IP2,MAPK8IP1

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

VDAC3,GPR37,UBA1,ATP5B,UCHL1,UQCRFS1,NDUFS7,NDUFS4,NDUFB10,NDUFB3,NDUFB4,NDUFB6,NDUFB2,NDUFA4,NDUFA8,NDUFA7,ATP5F1,PARK2,NDUFA1,SDHC

+ 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
BIOCARTA_PML_PATHWAY	17	8	2.4	0	0.0059
KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION	89	19	1.4	0	0.0059
BIOCARTA_IL3_PATHWAY	15	6	2.2	0.001	0.11
KEGG_GLYOXYLATE_AND_DICARBOXYLATE_METABOLISM	16	6	2.1	0.0015	0.12
KEGG_RNA_DEGRADATION	55	12	1.3	0.0022	0.13