Human Gene Set: LOCKWOOD_AMPLIFIED_IN_LUNG_CANCER


Standard name LOCKWOOD_AMPLIFIED_IN_LUNG_CANCER
Systematic name M4572
Brief description Overexpressed genes with amplified copy number across 27 non-small cell lung cancer (NSCLC) cell lines.
Full description or abstract Chromosomal translocation is the best-characterized genetic mechanism for oncogene activation. However, there are documented examples of activation by alternate mechanisms, for example gene dosage increase, though its prevalence is unclear. Here, we answered the fundamental question of the contribution of DNA amplification as a molecular mechanism driving oncogenesis. Comparing 104 cancer lines representing diverse tissue origins identified genes residing in amplification 'hotspots' and discovered an unexpected frequency of genes activated by this mechanism. The 3431 amplicons identified represent approximately 10 per hematological and approximately 36 per epithelial cancer genome. Many recurrently amplified oncogenes were previously known to be activated only by disease-specific translocations. The 135 hotspots identified contain 538 unique genes and are enriched for proliferation, apoptosis and linage-dependency genes, reflecting functions advantageous to tumor growth. Integrating gene dosage with expression data validated the downstream impact of the novel amplification events in both cell lines and clinical samples. For example, multiple downstream components of the EGFR-family-signaling pathway, including CDK5, AKT1 and SHC1, are overexpressed as a direct result of gene amplification in lung cancer. Our findings suggest that amplification is far more common a mechanism of oncogene activation than previously believed and that specific regions of the genome are hotspots of amplification.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18391978   Authors: Lockwood WW,Chari R,Coe BP,Girard L,Macaulay C,Lam S,Gazdar AF,Minna JD,Lam WL
Exact source Table 11S
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Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced

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