Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer Academic Article uri icon


MeSH Major

  • Gene Amplification
  • Lung Neoplasms
  • SOXB1 Transcription Factors
  • Small Cell Lung Carcinoma


  • Small-cell lung cancer (SCLC) is an exceptionally aggressive disease with poor prognosis. Here, we obtained exome, transcriptome and copy-number alteration data from approximately 53 samples consisting of 36 primary human SCLC and normal tissue pairs and 17 matched SCLC and lymphoblastoid cell lines. We also obtained data for 4 primary tumors and 23 SCLC cell lines. We identified 22 significantly mutated genes in SCLC, including genes encoding kinases, G protein-coupled receptors and chromatin-modifying proteins. We found that several members of the SOX family of genes were mutated in SCLC. We also found SOX2 amplification in ∼27% of the samples. Suppression of SOX2 using shRNAs blocked proliferation of SOX2-amplified SCLC lines. RNA sequencing identified multiple fusion transcripts and a recurrent RLF-MYCL1 fusion. Silencing of MYCL1 in SCLC cell lines that had the RLF-MYCL1 fusion decreased cell proliferation. These data provide an in-depth view of the spectrum of genomic alterations in SCLC and identify several potential targets for therapeutic intervention.


publication date

  • October 2012



  • Academic Article



  • eng

PubMed Central ID

  • PMC3557461

Digital Object Identifier (DOI)

  • 10.1038/ng.2405

PubMed ID

  • 22941189

Additional Document Info

start page

  • 1111

end page

  • 6


  • 44


  • 10