Combined microarray analysis of small cell lung cancer reveals altered apoptotic balance and distinct expression signatures of MYC family gene amplification

Y. H. Kim, L. Girard, C. P. Giacomini, P. Wang, T. Hernandez-Boussard, R. Tibshirani, J. D. Minna, J. R. Pollack

Research output: Contribution to journalArticle

131 Citations (Scopus)

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 ∼ 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.

Original languageEnglish (US)
Pages (from-to)130-138
Number of pages9
JournalOncogene
Volume25
Issue number1
DOIs
StatePublished - Jan 5 2006

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Gene Amplification
Small Cell Lung Carcinoma
Microarray Analysis
Genes
DNA
Oncogenes
Gene Expression
Comparative Genomic Hybridization
Oligonucleotide Array Sequence Analysis
Tumor Suppressor Genes
Lung Neoplasms
Carcinogenesis
Down-Regulation
Cell Line
Polymerase Chain Reaction

Keywords

  • Array CGH
  • DNA amplification
  • Expression profiling
  • MYC
  • Small cell lung cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Combined microarray analysis of small cell lung cancer reveals altered apoptotic balance and distinct expression signatures of MYC family gene amplification. / Kim, Y. H.; Girard, L.; Giacomini, C. P.; Wang, P.; Hernandez-Boussard, T.; Tibshirani, R.; Minna, J. D.; Pollack, J. R.

In: Oncogene, Vol. 25, No. 1, 05.01.2006, p. 130-138.

Research output: Contribution to journalArticle

Kim, Y. H. ; Girard, L. ; Giacomini, C. P. ; Wang, P. ; Hernandez-Boussard, T. ; Tibshirani, R. ; Minna, J. D. ; Pollack, J. R. / Combined microarray analysis of small cell lung cancer reveals altered apoptotic balance and distinct expression signatures of MYC family gene amplification. In: Oncogene. 2006 ; Vol. 25, No. 1. pp. 130-138.
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