EGAGenomicsAffymetrics_SNP_6.0-https://ega-archive.org/datasets/EGAD0001000052663EGA dataset EGAD00010000526EGASmall-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis. We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4±1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically relevant mutated genes. In all cases, we found evidence for inactivation of TP53 and RB1 and identified recurrent mutations in the CREBBP, EP300 and MLL genes that encode histone modifiers. Furthermore, we observed mutations in PTEN, SLIT2 and EPHA7, as well as focal amplifications of the FGFR1 tyrosine kinase gene. Finally, we detected many of the alterations found in humans in SCLC tumors from Tp53 and Rb1 double knockout mice. Our study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background.Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer.Peifer Martin M, Fernández-Cuesta Lynnette L, Sos Martin L ML, George Julie J, Seidel Danila D, Kasper Lawryn H LH, Plenker Dennis D, Leenders Frauke F, Sun Ruping R, Zander Thomas T, Menon Roopika R, Koker Mirjam M, Dahmen Ilona I, Müller Christian C, Di Cerbo Vincenzo V, Schildhaus Hans-Ulrich HU, Altmüller Janine J, Baessmann Ingelore I, Becker Christian C, de Wilde Bram B, Vandesompele Jo J, Böhm Diana D, Ansén Sascha S, Gabler Franziska F, Wilkening Ines I, Heynck Stefanie S, Heuckmann Johannes M JM, Lu Xin X, Carter Scott L SL, Cibulskis Kristian K, Banerji Shantanu S, Getz Gad G, Park Kwon-Sik KS, Rauh Daniel D, Grütter Christian C, Fischer Matthias M, Pasqualucci Laura L, Wright Gavin G, Wainer Zoe Z, Russell Prudence P, Petersen Iver I, Chen Yuan Y, Stoelben Erich E, Ludwig Corinna C, Schnabel Philipp P, Hoffmann Hans H, Muley Thomas T, Brockmann Michael M, Engel-Riedel Walburga W, Muscarella Lucia A LA, Fazio Vito M VM, Groen Harry H, Timens Wim W, Sietsma Hannie H, Thunnissen Erik E, Smit Egbert E, Heideman Daniëlle A M DA, Snijders Peter J F PJ, Cappuzzo Federico F, Ligorio Claudia C, Damiani Stefania S, Field John J, Solberg Steinar S, Brustugun Odd Terje OT, Lund-Iversen Marius M, Sänger Jörg J, Clement Joachim H JH, Soltermann Alex A, Moch Holger H, Weder Walter W, Solomon Benjamin B, Soria Jean-Charles JC, Validire Pierre P, Besse Benjamin B, Brambilla Elisabeth E, Brambilla Christian C, Lantuejoul Sylvie S, Lorimier Philippe P, Schneider Peter M PM, Hallek Michael M, Pao William W, Meyerson Matthew M, Sage Julien J, Shendure Jay J, Schneider Robert R, Büttner Reinhard R, Wolf Jürgen J, Nürnberg Peter P, Perner Sven S, Heukamp Lukas C LC, Brindle Paul K PK, Haas Stefan S, Thomas Roman K RKsmall cell cancer of the lung, SCLC1.Small Cell Carcinoma of the Lung, Oat Cell Carcinoma, small-cell lung cancer, poorly differentiated endocrine neoplasm, Oat Cell Lung Carcinoma, Small Cell Neuroendocrine Carcinoma of Lung, Genomes, Lung Oat Cell Carcinoma, Oat Cell Carcinomas, small cell lung carcinoma, oat cell lung carcinoma, Lung Small Cell Neuroendocrine Carcinoma, lung small cell neuroendocrine carcinoma, small cell neuroendocrine carcinoma of the lung, Small Cell Neuroendocrine Carcinoma of the Lung, Oat cell carcinoma of lung (disorder), whole genome, small cell carcinoma of lung, oat cell carcinoma of lung, small cell lung cancer, oat cell carcinoma (morphologic abnormality), SCLC - Small cell lung cancer, Mutations, SCLC, small cell neuroendocrine carcinoma of lung, small cell carcinoma of the lung, small cell cancer of the lung, small cell carcinoma of lung (disorder), oat cell carcinoma., oat cell carcinoma of the lung, Oat cell carcinoma of lung, lung small cell carcinoma, Oat Cell Carcinoma of the Lung, Small cell lung cancer, lung oat cell carcinoma, Small Cell Carcinoma of Lung, SCLC1small cell cancer of the lung, Small Cell Lung, CG11478, Dmel_CG6393, DmelCG42257, Oat Cell Lung Cancer, Carcinoma, cg11478, Small Cell Lung Cancer, 65K, CG6393, CG42257, Dmel_CG30327, snp, Small Cell Cancer Of The Lung, CG30327, SCLC1, Oat Cell Carcinoma of Lung.RB1, HTRX1, para Tyrosine, poorly differentiated endocrine neoplasm, Materials, Lung Oat Cell Carcinoma, Laboratory, lambdatop, HBGFR, oat cell lung carcinoma, Mus domesticus, DPTEN, dFGFR, dev, CASP-14, protein, RBF, Tumor, House Mouse, Tp53, Mutation Frequency, Cxxc7, CD331, small cell cancer of the lung, Mutations, x1fgfr, RBR, Histone H2b, Histone H2a, CEK, oat cell carcinoma of the lung, bbl, DFGF-R1, RB, rb, Mutation Frequencies, RETINOBLASTOMA PROTEIN, Eask, TEP1, Kinase, rbf, protein aggregate, Btl, DFR2, EHK-3, Fgf-r, FLG, Small Cell Carcinoma of the Lung, Prognoses, cek, Man (Taxonomy), Genomes, BCC7, pp110, 2-amino-3-(4-hydroxyphenyl)propanoic acid, 3-(p-Hydroxyphenyl)alanine, Rb, RTS, small cell neuroendocrine carcinoma of the lung, Swiss Mice, Hspy, fgfr-1, Y, oat cell carcinoma of lung, Dfr-2, flg, BTL/FGFR2, Tyr, Histone H5, Histone H4, Small cell lung cancer, Histone H7, CG7413, Malignancies, slit2-a, ATP Phosphotransferases, Frequency, Tk2, somatic mutation, Histone H1, mKIAA4141, ATP, Histone H3, Flt-2, Tumors, Base Pairings, small-cell lung cancer, retinoblastoma-related 1, Lung cancer, MLE, Oat Cell Carcinomas, Mll, MLL, rbf1, HRX, Modern, 2-Amino-3-(p-hydroxyphenyl)propionic acid, CASP14, mouse, KAT3B, KAT3A, Slil3, bFGF-R-1, retinoblastoma, para-Tyrosine, small cell carcinoma of lung, RETINOBLASTOMA 1, hereditary retinoblastoma, SCLC - Small cell lung cancer, Fgfr-1, Tyrosine, RSTS, Benign, PTEN3, XFGFR-1, PTEN1, Frequencies, DmelCG11680, mll, Mini-ICE, Genetic Materials, ATRBR1, bfy, rsts, mls, neoplasms, Genetic Material, E030015M03Rik, pRb, TET1-MLL, SLIL3, Mus musculus, Oat Cell Carcinoma, MEGF5, SLIL2, Transphosphorylases, Small Cell Neuroendocrine Carcinoma of Lung, Factors, DmelCG7413, Drad-1, Caspase-14 subunit p10, DmelCG32134, FGFR-1, mice, Prognostic, MMAC1, All1, WDSTS, L-isomer, Swiss Mouse, Exomes, Benign Neoplasms, INSDC_feature:gene, Caspase-14 subunit p19, XFGFRA2, PTENa, MICE, mKIAA4050, A730011L11, L isomer, Malignant Neoplasms, domesticus, p105-Rb, nap[ts], pulmonary, familial retinoblastoma, Material, c-fgr, P53, slil3, p44, bhy, Cistron, L-Tyrosine, Mouse, l(3)00208, EG:34F3.3, BZS, Rbf1, RBF1, kat3a, humans, Prognostic Factor, 2310035O07Rik, 3.4.22.-, A430090G16, localised, FBF, GLM2, EHK3, HRTFDS, small cell lung carcinoma, Neoplasms, p53, Benign Neoplasm, Gene, MLL|GAS7, mini-ICE, Prognostic Factors, RSTS2, protein-containing complex, small cell lung cancer, LFS1, E130320P19Rik, Malignant, autosomal dominant, dRBF, nap, MLL1A, KAL2, p300 HAT, Human, MHAM, eye cancer, Rate, Homo sapiens, House, Oat cell carcinoma of lung, Core Genome, AI463227, kal2, lung, Gene Products, OSRC, p300, Mus musculus domesticus, HH2, Small Cell Carcinoma of Lung, neoplasm, Mice, bfgfr, Phosphotransferase, Man, Histone H3.3, study, flt-2, 0844/01, Genetic, fgfr1, Malignancy, Swiss, BFGFR, FGFBR, Lung Small Cell Neuroendocrine Carcinoma, Accessory Genome, lung small cell neuroendocrine carcinoma, ALL-1, mak, Transphosphorylase, X1FGFR, DmelCG5671, oat cell carcinoma (morphologic abnormality), CG6714, Mll1, MLL1, Neoplasias, Trp53, EK11, small cell carcinoma of lung (disorder), 6430520K01, L Tyrosine, Base Pair, lung small cell carcinoma, FGFR, OGD, B430203M17Rik, lung oat cell carcinoma, TRP53, Tyrosin, AW208770, oat cell carcinoma, FGFR1, Cancer, FLT2, Oat Cell Lung Carcinoma, PTEN, Malignant Neoplasm, slit-2, protein complex, ogd, FLT-2, Proteins, D-FGFR, introduction., Small Cell Neuroendocrine Carcinoma of the Lung, dPten, Factor, dtk2, CG11680, pten, HEK11, Cistrons, MLL/GAS7, Pangenome, Histone, Phosphotransferases, Xp53, xfgfr1, N-SAM, small cell neuroendocrine carcinoma of lung, small cell carcinoma of the lung, dpten, fgf-r, native protein, tirosina, Mus, DmHD-311, CWS1, Protein, Mutation Rates, Neoplasm, PPP1R130, focal, flt2, background, dPTEN, Mutation, Rates, Base Pairs, histone modification site, Mmac, 10q23del, CG5671, Slit-2, Kinases, CXXC7, Slit-3, CBP, Rb-1, House Mice, Oat cell carcinoma of lung (disorder), Cancers, SLIT1, MFR, A130070J02Rik, Histone H1(s), Laboratory Mice, Protein Gene Products, Rb1, CG32134, SCLC, CT20816, Gene Proteins, DEC, Pan-genome, slit2, Modern Man, RETINOBLASTOMA-RELATED PROTEIN 1, RETINOBLASTOMA-RELATED, cbp, TRX1, Oat Cell Carcinoma of the Lung, HD-311, RbF, Dtk2, trilateral, SCLC1, Laboratory Mouse, Neoplasia, crebbpfalseSCLC_6.0 - samplesSNP 6.0 arrays of small cell lung cancer2017-07-26 15:39:25EGAD00010000526960622941188EGAC00001000064EGAS00001000299