EGAGenomicsIllumina HiSeq 2000, Illumina_2.5MOtherhttps://ega-archive.org/studies/EGAS00001000334EGAEGA study EGAS00001000334Whole genome sequencing of SCLC tumor/normal samplesTitle not providedRNA sequencing of SCLC tumor/normal sample pairs and cell linesExome capture sequencing of SCLC tumor/normal pairs and cell linesrestrictedEGASmall-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.Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer.Rudin Charles M CM, Durinck Steffen S, Stawiski Eric W EW, Poirier John T JT, Modrusan Zora Z, Shames David S DS, Bergbower Emily A EA, Guan Yinghui Y, Shin James J, Guillory Joseph J, Rivers Celina Sanchez CS, Foo Catherine K CK, Bhatt Deepali D, Stinson Jeremy J, Gnad Florian F, Haverty Peter M PM, Gentleman Robert R, Chaudhuri Subhra S, Janakiraman Vasantharajan V, Jaiswal Bijay S BS, Parikh Chaitali C, Yuan Wenlin W, Zhang Zemin Z, Koeppen Hartmut H, Wu Thomas D TD, Stern Howard M HM, Yauch Robert L RL, Huffman Kenneth E KE, Paskulin Diego D DD, Illei Peter B PB, Varella-Garcia Marileila M, Gazdar Adi F AF, de Sauvage Frederic J FJ, Bourgon Richard R, Minna John D JD, Brock Malcolm V MV, Seshagiri Somasekar SfalseGenentech Small Cell Lung Cancer (SCLC) ScreenExome capture, RNA-Seq, whole genome sequencing of set of Small Cell Lung Cancer samples.2019-10-31 12:52:15EGAS00001000334960622941189EGAD00001000223EGAD00001000221EGAD00001000222EGAD00010000276EGAD00010000278EGAC00001000055