Systematic name M12053
Brief description Genes within amplicon 22q13 identified in a copy number alterations study of 191 breast tumor samples.
Full description or abstract A single cancer cell contains large numbers of genetic alterations that in combination create the malignant phenotype. However, whether amplified and mutated genes form functional and physical interaction networks that could explain the selection for cells with combined alterations is unknown. To investigate this issue, we characterized copy number alterations in 191 breast tumors using dense single nucleotide polymorphism arrays and identified 1,747 genes with copy number gain organized into 30 amplicons. Amplicons were distributed unequally throughout the genome. Each amplicon had distinct enrichment pattern in pathways, networks, and molecular functions, but genes within individual amplicons did not form coherent functional units. Genes in amplicons included all major tumorigenic pathways and were highly enriched in breast cancer-causative genes. In contrast, 1,188 genes with somatic mutations in breast cancer were distributed randomly over the genome, did not represent a functionally cohesive gene set, and were relatively less enriched in breast cancer marker genes. Mutated and gained genes did not show statistically significant overlap but were highly synergistic in populating key tumorigenic pathways including transforming growth factor beta, WNT, fibroblast growth factor, and PIP3 signaling. In general, mutated genes were more frequently upstream of gained genes in transcription regulation signaling than vice versa, suggesting that mutated genes are mainly regulators, whereas gained genes are mostly regulated. ESR1 was the major transcription factor regulating amplified but not mutated genes. Our results support the hypothesis that multiple genetic events, including copy number gains and somatic mutations, are necessary for establishing the malignant cell phenotype.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 19010930   Authors: Nikolsky Y,Sviridov E,Yao J,Dosymbekov D,Ustyansky V,Kaznacheev V,Dezso Z,Mulvey L,Macconaill LE,Winckler W,Serebryiskaya T,Nikolskaya T,Polyak K
Exact source Suppl. Excel File 1S: 22q13
Related gene sets (show 30 additional gene sets from the source publication)

(show 12 gene sets from the same authors)
External links  
Organism Homo sapiens
Contributed by Jessica Robertson (Broad Institute)
Source platform EntrezGeneIds
Dataset references  
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 17 genes
Gene families Categorize these 17 genes by gene family
Show members (show 17 members mapped to 17 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.