EGAGenomicsAffymetrix SNP 6.0https://ega-archive.org/datasets/EGAD0001000055854EGA dataset EGAD00010000558EGAWe have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.Comprehensive genomic profiles of small cell lung cancer.George Julie J, Lim Jing Shan JS, Jang Se Jin SJ, Cun Yupeng Y, Ozretić Luka L, Kong Gu G, Leenders Frauke F, Lu Xin X, Fernández-Cuesta Lynnette L, Bosco Graziella G, Müller Christian C, Dahmen Ilona I, Jahchan Nadine S NS, Park Kwon-Sik KS, Yang Dian D, Karnezis Anthony N AN, Vaka Dedeepya D, Torres Angela A, Wang Maia Segura MS, Korbel Jan O JO, Menon Roopika R, Chun Sung-Min SM, Kim Deokhoon D, Wilkerson Matt M, Hayes Neil N, Engelmann David D, Pützer Brigitte B, Bos Marc M, Michels Sebastian S, Vlasic Ignacija I, Seidel Danila D, Pinther Berit B, Schaub Philipp P, Becker Christian C, Altmüller Janine J, Yokota Jun J, Kohno Takashi T, Iwakawa Reika R, Tsuta Koji K, Noguchi Masayuki M, Muley Thomas T, Hoffmann Hans H, Schnabel Philipp A PA, Petersen Iver I, Chen Yuan Y, Soltermann Alex A, Tischler Verena V, Choi Chang-min CM, Kim Yong-Hee YH, Massion Pierre P PP, Zou Yong Y, Jovanovic Dragana D, Kontic Milica M, Wright Gavin M GM, Russell Prudence A PA, Solomon Benjamin B, Koch Ina I, Lindner Michael M, Muscarella Lucia A LA, la Torre Annamaria A, Field John K JK, Jakopovic Marko M, Knezevic Jelena J, Castaños-Vélez Esmeralda E, Roz Luca L, Pastorino Ugo U, Brustugun Odd-Terje OT, Lund-Iversen Marius M, Thunnissen Erik E, Köhler Jens J, Schuler Martin M, Botling Johan J, Sandelin Martin M, Sanchez-Cespedes Montserrat M, Salvesen Helga B HB, Achter Viktor V, Lang Ulrich U, Bogus Magdalena M, Schneider Peter M PM, Zander Thomas T, Ansén Sascha S, Hallek Michael M, Wolf Jürgen J, Vingron Martin M, Yatabe Yasushi Y, Travis William D WD, Nürnberg Peter P, Reinhardt Christian C, Perner Sven S, Heukamp Lukas L, Büttner Reinhard R, Haas Stefan A SA, Brambilla Elisabeth E, Peifer Martin M, Sage Julien J, Thomas Roman K RKsmall cell cancer of the lung, CG11478, Dmel_CG6393, DmelCG42257, snp, cg11478, CG30327, SCLC1, 65K, CG6393, CG42257, Dmel_CG30327.small cell cancer of the lung, Small Cell Lung, Oat Cell Lung Cancer, Carcinoma, Small Cell Cancer Of The Lung, Small Cell Lung Cancer, SCLC1, Oat Cell Carcinoma of Lung.small 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, Networks, Forms, MGC130048, Materials, xnotch, Kinship, PhrB photolyase activity, Activity, Laboratory, Mus domesticus, cD1, A4, CASP-14, RBF, Tumor, pigmented epithelium, CCND1 Protein, House Mouse, Tp53, small cell cancer of the lung, Proto Oncogene Products bcl 1, Mutations, dmTAF[[II]]230, RBR, c-bcl-1, Biological Processes, Biological Phenomenon, NOTCH, Biological, bbl, RB, rb, Life Cycle, 3, RETINOBLASTOMA PROTEIN, Kinase, NUP96, rbf, Phenomenon, notch, epithelium, IKKg, Family Life Cycle, KEY, Key, gamma sarcoglycan, Lung Cancer, Man (Taxonomy), Kinship Network, Gene Expressions, TFIID TAF250, Genomes, BCC7, cel, pp110, Rb, hypoplasia, CycD1, pigmented retina, Swiss Mice, Lung Cancers, Ax, DNA cyclobutane dipyrimidine photolyase activity, Tp73, SUPPRESSOR OF AUXIN RESISTANCE 3, notch1-a, Proto-Oncogene Products, malignant neoplasm, co, signaling process, Xotch, ccnd1a, Therapies, gamma-sarcoglycan, Shattering, Malignancies, CG7413, house mouse, Family Life Cycles, ATP Phosphotransferases, somatic mutation, NECD, EG:140G11.1, ATP, l(1)N, single organism signaling, Tumors, swb, Therapy, PRE, retinoblastoma-related 1, dTAF[[II]]230, Chp, Process, Co, rbf1, bcl-1 Proto-Oncogene Proteins, Modern, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, SG-gamma, mouse, CASP14, TAF200, Cancer of Lung, retinoblastoma, Proto Oncogene Protein bcl 1, TAFII-250, TAF250/230, RETINOBLASTOMA 1, hereditary retinoblastoma, DmIKKgamma, TAFII250, Proto Oncogene Proteins c bcl 1, Benign, retinal pigment, dIKK, shd, Mini-ICE, Kenny, dipyrimidine photolyase (photosensitive), ATRBR1, Genetic Materials, sarcoglycan, bfy, Chromosome Shattering, Biological Process, Filiation, fa, retinal pigment layer, bcl-1, Genetic Material, activation, pRb, xnotch1, Mus musculus, Biologic Phenomena, Transphosphorylases, c-bcl-1 Proteins, DmelCG7413, death rate, Caspase-14 subunit p10, mice, Swiss Mouse, IKK-gamma, Benign Neoplasms, bcl 1 Proto Oncogene Proteins, INSDC_feature:gene, Caspase-14 subunit p19, deltaNp73, whole genome, CG17603, gamma (35kDa dystrophin-associated glycoprotein), MICE, TAF[[II]], Treatments, human, Malignant Neoplasms, domesticus, Life Cycles, p105-Rb, phr A photolyase activity, DMDA, DNA-photoreactivating enzyme, DmelCG16910, Taf250, familial retinoblastoma, Chromosome, Patient, clone 1.12, Material, SR3-5, 35kD dystrophin-associated glycoprotein, P53, p44, Proto-Oncogene Protein bcl-1, bhy, Cistron, notch-1, Mouse, Cancer of the Lung, TAN1, EG:34F3.3, other neoplasm, n[fah], TAF230, Rbf1, RBF1, bcl1 Proto-Oncogene Proteins, Malignant Neoplasms., TAp73, 3.4.22.-, d230, biological signaling, Lung, human being, SGCG_HUMAN, Family Member, FBF, Processes, Neoplasms, p53, Benign Neoplasm, EG:163A10.2, number, Gene, dTAFII250, mini-ICE, PRAD1 Protein, Network, photoreactivating enzyme activity, EfW1, Malignant, LFS1, autosomal dominant, dRBF, TYPE, dIKK-gamma, Human, DAGA4, eye cancer, reduced, Homo sapiens, dmTAF1, House, Taf230, Core Genome, P73, DmIKK-gamma, 35DAG, OSRC, Mus musculus domesticus, stratum pigmentosa retinae, tiny, l(1)3Cb, dmIKKgamma, Pulmonary Cancer, MAM, gamma-SG, IKK[[gamma]], SCG3, Mice, Man, Trp73, Phosphotransferase, Pulmonary, l(1)Ax, TAF250, bcl 1 Proto Oncogene Products, study, Taf200, MOS3, dTAF[[II]]250, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Genetic, Malignancy, PRECOCIOUS, Research, cell, Swiss, p73, DmelCG3936, Accessory Genome, Chromothripses, Cyl-1, F23A5.3, Taf1p, dNotch, Transphosphorylase, Proto-Oncogene Proteins, Expressions, Neoplasias, dTAF250, Trp53, Lung Neoplasm, bcl1, IKK, time of survival, Clients, Chromosome Shatterings, prad1, Expression, TRP53, Kinship Networks, TAF, NICD, BCL1, Family, ccnd1, CT13012, F23A5_3, Biologic, Cancer, small, 16-178, 16-55, D11S287E, TAF[[II]]250, Pulmonary Neoplasms, Malignant Neoplasm, Family Research, 35 kDa dystrophin-associated glycoprotein, Proto-Oncogene Protein, l(3)84Ab, bcl-1 Proto-Oncogene Products, BG:DS00004.13, anon-EST:Liang-1.12, Cistrons, Pangenome, Client, Cell, Phosphotransferases, SGCG, Xp53, LGMD2C, dTAF230, PRAD1, Family Members, IKKgamma, MODIFIER OF SNC1, MT, survival, Mus, p230, spl, U21B31, deoxyribonucleic photolyase activity, Phenomena, Neoplasm, TAF[[II]]250/230, PPP1R130, TFIID, AI327039, 1.1, nd, Proto-Oncogene Proteins c-bcl-1, c bcl 1 Proteins, Taf[[II]]250, primary cancer, RPE, TAF[[II]]230, DMDA1, underdeveloped, photolyase activity, Kinases, Dmikkgamma, Pulmonary Neoplasm, Rb-1, Proto-Oncogene Products bcl-1, House Mice, TAF[II]250, Cancers, CG16910, malignant tumor, signalling, p. pigmentosa retinae, Laboratory Mice, Rb1, Pan-genome, DmelCG17603, signalling process, Therapeutic, Families, Modern Man, SCARMD2, cardinality, RETINOBLASTOMA-RELATED PROTEIN 1, RETINOBLASTOMA-RELATED, Treatment, Pulmonary Cancers, deoxyribonucleate pyrimidine dimer lyase (photosensitive), RbF, CG3936, trilateral, bcl1 Proto Oncogene Proteins, Relatives, SCLC1, Laboratory Mouse, General activity, Neoplasia, TAF1falseSCLC_SNP_6.0 - samplesSNP 6.0 arrays of small cell lung cancer2017-07-26 15:39:26EGAD00010000558960626168399EGAC00001000064EGAS00001000925