Association of mutation, copy number alteration, and subtype markers with pathways

Lung Squamous Cell Carcinoma (Primary solid tumor)

23 May 2013 | analyses__2013_05_23

Maintainer Information

Citation Information

Maintained by Spring Yingchun Liu (Broad Institute)

Cite as Broad Institute TCGA Genome Data Analysis Center (2013): Association of mutation, copy number alteration, and subtype markers with pathways. Broad Institute of MIT and Harvard. doi:10.7908/C1F47M5T

- 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 14 genes with significant mutation (Q value <= 0.1) and 254 genes with significant copy number alteration (Q value <= 0.25). The identified marker genes (Q value <= 0.01 or within top 2000) are 1094 for subtype 1, 1094 for subtype 2, 1094 for subtype 3, 1094 for subtype 4. Pathways significantly enriched with these genes (Q value <= 0.01) are identified :

7 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

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

16 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_G1_PATHWAY	28	5	3.8	0	0.0056
BIOCARTA_TEL_PATHWAY	18	4	4.1	0.0001	0.0056
BIOCARTA_ARF_PATHWAY	17	4	4.2	0.0001	0.0056
KEGG_UBIQUITIN_MEDIATED_PROTEOLYSIS	137	9	2.4	0.0001	0.0056
KEGG_RIBOSOME	87	7	2.7	0.0001	0.0074

List of CNV_Mut genes in this pathway

CDKN2A,TFDP1,SKP2,TP53,RB1

List of CNV_Mut genes in this pathway

XRCC5,TP53,RB1,PTEN

List of CNV_Mut genes in this pathway

TP53,RB1,CDKN2A,PIK3CA

List of CNV_Mut genes in this pathway

SAE1,CUL1,SKP2,KEAP1,FBXW7,UBE2L3,UBE2F,UBE2S,CUL4A

List of CNV_Mut genes in this pathway

RPL18,RPS19,RPS16,RPL37,RPL38,RPL28,MRPL23

+ 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_ENDOCYTOSIS	183	21	1.3	0.0001	0.032
KEGG_TIGHT_JUNCTION	134	17	1.4	0.0002	0.032
KEGG_ADHERENS_JUNCTION	75	10	1.5	0.0026	0.28
KEGG_GLYCOSAMINOGLYCAN_BIOSYNTHESIS_CHONDROITIN_SULFATE	22	5	2.2	0.0034	0.28
BIOCARTA_MPR_PATHWAY	34	6	1.9	0.0052	0.35

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

HRAS,VPS4B,EGFR,ARRB1,SH3GL1,ERBB3,ASAP2,TRAF6,AP2M1,PARD6A,NEDD4,IL8RA,IL8RB,BRD8,LDLRAP1,ADRB2,EEA1,KIT,VPS36,TFRC,RNF41

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

HRAS,OCLN,AMOTL1,CSNK2A1,F11R,CSDA,CGN,MYL5,GNAI1,PPP2R2C,PARD6A,CLDN7,CLDN9,PPP2R2A,CLDN16,MLLT4,TJP3

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

IQGAP1,CSNK2A1,EGFR,MAPK1,TCF7L1,PVRL4,MLLT4,SMAD3,SNAI1,FYN

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

CHST3,XYLT2,CHST11,CHST14,CHSY1

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

HRAS,GNAI1,PAQR7,ACTR3,ACTR2,MAPK1

+ 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_AGR_PATHWAY	36	11	1.8	0.0002	0.023
KEGG_DRUG_METABOLISM_OTHER_ENZYMES	51	13	1.6	0.0002	0.023
BIOCARTA_INTRINSIC_PATHWAY	23	8	2	0.0005	0.034
KEGG_NEUROTROPHIN_SIGNALING_PATHWAY	126	23	1	0.0005	0.034
BIOCARTA_AMI_PATHWAY	20	7	2	0.001	0.049

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

ITGB1,PXN,CDC42,DMD,PAK1,NRG2,DVL1,LAMA2,MAPK1,PSG1,MAPK3

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

CYP3A5,IMPDH1,UMPS,UGT2B10,UGT2B15,XDH,TK1,UCK1,UCK2,UGT2B28,UPB1,TPMT,DPYD

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

F12,F10,COL4A6,COL4A5,PROC,F5,FGA,FGB

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

MAGED1,BRAF,IRS1,MAPK1,MAPK3,RIPK2,IRAK4,ARHGDIB,PLCG1,ABL1,CDC42,CRKL,ZNF274,CALML3,CAMK2B,CALML5,PIK3R3,YWHAB,RPS6KA3,MAPK12,RPS6KA1,RPS6KA2,YWHAQ

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

F10,F7,COL4A6,COL4A5,PROC,FGA,FGB

+ 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_METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450	70	8	2.2	0.0003	0.11
KEGG_DRUG_METABOLISM_CYTOCHROME_P450	72	7	2	0.002	0.13
KEGG_ECM_RECEPTOR_INTERACTION	84	8	1.9	0.0012	0.13
KEGG_ADHERENS_JUNCTION	75	7	1.9	0.0023	0.13
KEGG_HYPERTROPHIC_CARDIOMYOPATHY_HCM	85	8	1.9	0.0011	0.13