The landscape of somatic copy-number alteration across human cancers
Rameen Beroukhim,Craig H. Mermel,Craig H. Mermel,Dale Porter,Guo Wei,Soumya Raychaudhuri,Soumya Raychaudhuri,Jerry Donovan,Jordi Barretina,Jordi Barretina,Jesse S. Boehm,Jennifer Dobson,Jennifer Dobson,Mitsuyoshi Urashima,Kevin T. Mc Henry,Reid M. Pinchback,Azra H. Ligon,Yoon Jae Cho,Leila Haery,Leila Haery,Heidi Greulich,Michael R. Reich,Wendy Winckler,Michael S. Lawrence,Barbara A. Weir,Barbara A. Weir,Kumiko E. Tanaka,Kumiko E. Tanaka,Derek Y. Chiang,Derek Y. Chiang,Derek Y. Chiang,Adam J. Bass,Adam J. Bass,Adam J. Bass,Alice Loo,Carter Hoffman,Carter Hoffman,John R. Prensner,John R. Prensner,Ted Liefeld,Qing Gao,Derek Yecies,Sabina Signoretti,Sabina Signoretti,Elizabeth A. Maher,Frederic J. Kaye,Hidefumi Sasaki,Joel E. Tepper,Jonathan A. Fletcher,Josep Tabernero,José Baselga,Ming-Sound Tsao,Francesca Demichelis,Mark A. Rubin,Pasi A. Jänne,Pasi A. Jänne,Mark J. Daly,Mark J. Daly,Carmelo Nucera,Ross L. Levine,Benjamin L. Ebert,Benjamin L. Ebert,Benjamin L. Ebert,Stacey Gabriel,Anil K. Rustgi,Cristina R. Antonescu,Marc Ladanyi,Anthony Letai,Levi A. Garraway,Levi A. Garraway,Massimo Loda,Massimo Loda,David G. Beer,Lawrence D. True,Aikou Okamoto,Scott L. Pomeroy,Samuel Singer,Todd R. Golub,Todd R. Golub,Todd R. Golub,Eric S. Lander,Eric S. Lander,Eric S. Lander,Gad Getz,William R. Sellers,Matthew Meyerson,Matthew Meyerson +86 more
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TLDR
It is demonstrated that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival, and a large majority of SCNAs identified in individual cancer types are present in several cancer types.Abstract:
A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.read more
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Role of DNA secondary structures in fragile site breakage along human chromosome 10
TL;DR: The role of DNA secondary structures in common fragile site instability is supported, a systematic method for their identification is provided and a mechanism by which DNA secondary structure formation can lead to human disease is suggested.
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3D genome and its disorganization in diseases.
TL;DR: The various 3D genome technologies are introduced, with a focus on their application to cancer and disease research, as well as future developments to extend their utility.
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An integrated computational and experimental study uncovers FUT9 as a metabolic driver of colorectal cancer.
Noam Auslander,Chelsea E. Cunningham,Behzad M. Toosi,Emily J McEwen,Keren Yizhak,Frederick S. Vizeacoumar,Sreejit Parameswaran,Nir Gonen,Tanya Freywald,Kalpana Kalyanasundaram Bhanumathy,Andrew Freywald,Franco J. Vizeacoumar,Eytan Ruppin +12 more
TL;DR: It is suggested that FUT9's inhibition may attenuate tumor‐initiating cells (TICs) that are known to dominate tumorspheres and early tumor growth, but promote bulk tumor cells.
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Clinical implementation of integrated whole-genome copy number and mutation profiling for glioblastoma.
Shakti Ramkissoon,Wenya Linda Bi,Steven E. Schumacher,Lori A. Ramkissoon,Sam Haidar,David S. Knoff,Adrian M. Dubuc,Loreal Brown,Margot Burns,Jane Cryan,Malak Abedalthagafi,Yun Jee Kang,Nikolaus Schultz,David A. Reardon,Eudocia Q. Lee,Mikael L. Rinne,Andrew D. Norden,Lakshmi Nayak,Sandra Ruland,Lisa Doherty,Debra LaFrankie,M.C. Horvath,Ayal A. Aizer,Andrea L. Russo,Nils D. Arvold,Elizabeth B. Claus,Ossama Al-Mefty,Mark D. Johnson,Alexandra J. Golby,Ian F. Dunn,E. Antonio Chiocca,Lorenzo Trippa,Sandro Santagata,Rebecca D. Folkerth,Philip W. Kantoff,Barrett J. Rollins,Neal I. Lindeman,Patrick Y. Wen,Azra H. Ligon,Rameen Beroukhim,Brian M. Alexander,Keith L. Ligon +41 more
TL;DR: Combined use of multiplexed copy number and mutation detection from FFPE samples in the clinical setting can efficiently replace singleton tests for clinical diagnosis and prognosis in most settings.
Journal ArticleDOI
ACE: absolute copy number estimation from low-coverage whole-genome sequencing data.
TL;DR: An analytical tool for Absolute Copy number Estimation, ACE, is described, which scales relative copy number signals from chromosomal segments to optimally fit absolute copy numbers, without the need for additional genetic information, such as SNP data.
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Comprehensive genomic characterization defines human glioblastoma genes and core pathways
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TL;DR: The interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated gliobeasts, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
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The clonal evolution of tumor cell populations
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In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector
Luigi Naldini,Ulrike Blömer,Philippe Gallay,Daniel S. Ory,Richard C. Mulligan,Fred H. Gage,Inder M. Verma,Didier Trono +7 more
TL;DR: The ability of HIV-based viral vectors to deliver genes in vivo into nondividing cells could increase the applicability of retroviral vectors in human gene therapy.
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Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection
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