Journal
NATURE GENETICS
Volume 44, Issue 10, Pages 1111-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2405
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Funding
- Burroughs Wellcome Fund
- Flight Attendant Medical Research Institute
- Johns Hopkins Specialized Programs of Research Excellence (SPORE) NCI [P50CA058184]
- Colorado SPORE NCI [P50 CA058187]
- University of Texas SPORE NCI [P50CA70907]
- Coordenacao de Aperfeicoamento de Passoal de Nivel Superior (CAPES) Foundation
- Ministry of Education of Brazil
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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 similar to 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.
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