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- Title
Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer.
- Authors
Rudin, Charles M; Durinck, Steffen; Stawiski, Eric W; Poirier, John T; Modrusan, Zora; Shames, David S; Bergbower, Emily A; Guan, Yinghui; Shin, James; Guillory, Joseph; Rivers, Celina Sanchez; Foo, Catherine K; Bhatt, Deepali; Stinson, Jeremy; Gnad, Florian; Haverty, Peter M; Gentleman, Robert; Chaudhuri, Subhra; Janakiraman, Vasantharajan; Jaiswal, Bijay S
- Abstract
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.
- Subjects
SMALL cell lung cancer; GENE amplification; GENETIC transcription; TISSUES; CHROMATIN; G protein coupled receptors; PROGNOSIS
- Publication
Nature Genetics, 2012, Vol 44, Issue 10, p1111
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.2405