Gene Set: KIM_MYCN_AMPLIFICATION_TARGETS_UP

Standard name KIM_MYCN_AMPLIFICATION_TARGETS_UP
Systematic name M18532
Brief description Genes positively correlated with amplifications of MYCN [GeneID=4613] in the SCLC (small cell lung cancer) cell lines.
Full description or abstract DNA amplifications and deletions frequently contribute to the development and progression of lung cancer. To identify such novel alterations in small cell lung cancer (SCLC), we performed comparative genomic hybridization on a set of 24 SCLC cell lines, using cDNA microarrays representing approximately 22,000 human genes (providing an average mapping resolution of <70 kb). We identified localized DNA amplifications corresponding to oncogenes known to be amplified in SCLC, including MYC (8q24), MYCN (2p24) and MYCL1 (1p34). Additional highly localized DNA amplifications suggested candidate oncogenes not previously identified as amplified in SCLC, including the antiapoptotic genes TNFRSF4 (1p36), DAD1 (14q11), BCL2L1 (20q11) and BCL2L2 (14q11). Likewise, newly discovered PCR-validated homozygous deletions suggested candidate tumor-suppressor genes, including the proapoptotic genes MAPK10 (4q21) and TNFRSF6 (10q23). To characterize the effect of DNA amplification on gene expression patterns, we performed expression profiling using the same microarray platform. Among our findings, we identified sets of genes whose expression correlated with MYC, MYCN or MYCL1 amplification, with surprisingly little overlap among gene sets. While both MYC and MYCN amplification were associated with increased and decreased expression of known MYC upregulated and downregulated targets, respectively, MYCL1 amplification was associated only with the latter. Our findings support a role of altered apoptotic balance in the pathogenesis of SCLC, and suggest that MYC family genes might affect oncogenesis through distinct sets of targets, in particular implicating the importance of transcriptional repression.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16116477   Authors: Kim YH,Girard L,Giacomini CP,Wang P,Hernandez-Boussard T,Tibshirani R,Minna JD,Pollack JR
Exact source Table 3S: positively correlated with MYCN
Related gene sets (show 5 additional gene sets from the source publication)

(show 15 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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Compendia expression profiles Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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