Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer
Top Cited Papers
Open Access
- 2 September 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 44 (10), 1111-1116
- https://doi.org/10.1038/ng.2405
Abstract
Sekar Seshagiri and colleagues report exome, transcriptome and copy-number alteration data in small-cell lung cancer. The authors find SOX2 amplification in 27% of samples and also identify a recurrent RFL-MYCL1 fusion. 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.Keywords
This publication has 50 references indexed in Scilit:
- Recurrent R-spondin fusions in colon cancerNature, 2012
- Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancerNature Genetics, 2012
- Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cellsProceedings of the National Academy of Sciences of the United States of America, 2012
- Functionally recurrent rearrangements of the MAST kinase and Notch gene families in breast cancerNature Medicine, 2011
- A framework for variation discovery and genotyping using next-generation DNA sequencing dataNature Genetics, 2011
- Improving the Assessment of the Outcome of Nonsynonymous SNVs with a Consensus Deleteriousness Score, CondelAmerican Journal of Human Genetics, 2011
- Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung CancerThe New England Journal of Medicine, 2010
- A small-cell lung cancer genome with complex signatures of tobacco exposureNature, 2009
- SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomasNature Genetics, 2009
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006