Lung Adenocarcinoma: 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 114 genes with significant mutation (Q value <= 0.1) and 540 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 18 for subtype 1. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

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

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

- 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_WNT_SIGNALING_PATHWAY	151	21	2.2	0	0
KEGG_PARKINSONS_DISEASE	130	14	2	0	0.0014
KEGG_CITRATE_CYCLE_TCA_CYCLE	32	7	2.9	0	0.0034
KEGG_OXIDATIVE_PHOSPHORYLATION	133	12	1.8	0.0002	0.019
KEGG_ALZHEIMERS_DISEASE	167	14	1.5	0.0004	0.024

List of CNV_Mut genes in this pathway

MAPK9,PPP2R5E,RAC1,DVL2,DVL3,SMAD4,SMAD2,PRICKLE2,RHOA,PPP2R1B,TBL1XR1,SUMO1,PSEN1,PPP2CA,PPP2CB,PPP3CC,CHP,FBXW11,CSNK1A1,GPI,FZD5

List of CNV_Mut genes in this pathway

UBA7,COX6B1,COX6A1,PINK1,UQCRFS1,NDUFS6,CASP3,ATP5O,ATP5H,NDUFB5,NDUFA9,PARK7,SDHB,SDHD

List of CNV_Mut genes in this pathway

IDH1,PDHA2,SUCLG2,DLAT,PCK1,SDHB,SDHD

List of CNV_Mut genes in this pathway

COX6B1,COX6A1,UQCRFS1,NDUFS6,ATP5O,ATP5H,ATP6V1H,NDUFB5,NDUFA9,SDHB,SDHD,ATP6V0A2

List of CNV_Mut genes in this pathway

COX6B1,COX6A1,UQCRFS1,NDUFS6,CASP3,ATP5O,ATP5H,PSEN1,NDUFB5,PPP3CC,CHP,NDUFA9,SDHB,SDHD

+ 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
BIOCARTA_BCR_PATHWAY	35	1	5.2	0.027	0.78
BIOCARTA_HDAC_PATHWAY	30	1	5.4	0.023	0.78
BIOCARTA_CALCINEURIN_PATHWAY	19	1	6.1	0.014	0.78
BIOCARTA_FCER1_PATHWAY	39	1	5	0.03	0.78
BIOCARTA_FMLP_PATHWAY	37	1	5.1	0.029	0.78