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
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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Pathogenic Role of the CRL4 Ubiquitin Ligase in Human Disease
Jennifer Lee,Pengbo Zhou +1 more
TL;DR: This focused review will summarize the current knowledge of the two CUL4 family members in the pathogenesis of human malignancy and neuronal disease, and discuss their potential as new targets for cancer prevention and therapeutic intervention.
Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia
Jennifer R. Brown,Megan Hanna,Bethany Tesar,Lillian Werner,Nathalie Pochet,John M. Asara,Yaoyu E. Wang,P. Dal Cin,Stacey M. Fernandes,Christina Thompson,Laura E. MacConaill,Catherine J. Wu,Y. Van de Peer,Mick Correll,Aviv Regev,Donna Neuberg,Arnold S. Freedman +16 more
TL;DR: High-resolution genomic analysis of chronic lymphocytic leukemia reveals a stable genotype, with a median of only 1 somatic CNA per sample, and implicates amplifications of 3q26 focused on PIK3CA and 8q24 focused on MYC in CLL.
Journal ArticleDOI
Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer
TL;DR: The state-of-the-art in the development of drugs targeting Bcl-2 anti-apoptotic proteins is discussed to highlight the potential of their application as single agents or in combination for improving anti-cancer therapy, focusing in particular on solid tumors.
Journal ArticleDOI
A conditional piggyBac transposition system for genetic screening in mice identifies oncogenic networks in pancreatic cancer
Roland Rad,Lena Rad,Wei Wang,Alexander Strong,Hannes Ponstingl,Iraad F. Bronner,Matthew Mayho,Katja Steiger,Julia Weber,Maren Hieber,Christian Veltkamp,Stefan Eser,Ulf Geumann,Rupert Öllinger,Magdalena Zukowska,Maxim Barenboim,Roman Maresch,Juan Cadiñanos,Mathias J Friedrich,Ignacio Varela,Fernando Constantino-Casas,Aaron L. Sarver,Jelle ten Hoeve,Haydn M. Prosser,Barbara Seidler,Judith Bauer,Mathias Heikenwalder,Emmanouil Metzakopian,Anne Krug,Ursula Ehmer,Günter Schneider,Thomas Knösel,Petra Rümmele,Daniela Aust,Robert Grützmann,Christian Pilarsky,Zemin Ning,Lodewyk F. A. Wessels,Roland M. Schmid,Michael A. Quail,George S. Vassiliou,Irene Esposito,Pentao Liu,Dieter Saur,Allan Bradley +44 more
TL;DR: A conditional piggyBac transposition system in mice is described and the discovery of large sets of new cancer genes through a pancreatic insertional mutagenesis screen is reported, demonstrating the power of genetic screening to discover cancer drivers that are difficult to identify by other approaches to cancer genome analysis.
Journal ArticleDOI
A survey of intragenic breakpoints in glioblastoma identifies a distinct subset associated with poor survival
Siyuan Zheng,Jun Fu,Rahulsimham Vegesna,Yong Mao,Lindsey Heathcock,Wandaliz Torres-Garcia,Ravesanker Ezhilarasan,Shuzhen Wang,Aaron McKenna,Lynda Chin,Cameron Brennan,W. K. Alfred Yung,John N. Weinstein,Kenneth D. Aldape,Erik P. Sulman,Ken Chen,Dimpy Koul,Roeland Verhaak +17 more
TL;DR: A previously underappreciated genomic mechanism of gene deregulation that can confer growth advantages on tumor cells and may generate cancer-specific vulnerabilities in subsets of GBM is uncovered.
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Yoav Benjamini,Yosef Hochberg +1 more
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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.
Journal ArticleDOI
The clonal evolution of tumor cell populations
TL;DR: Each patient's cancer may require individual specific therapy, and even this may be thwarted by emergence of a genetically variant subline resistant to the treatment, which should be directed toward understanding and controlling the evolutionary process in tumors before it reaches the late stage usually seen in clinical cancer.
Journal ArticleDOI
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.
Journal ArticleDOI
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection
Cheng Li,Wing Hung Wong +1 more
TL;DR: A statistical model is proposed for the probe-level data, and model-based estimates for gene expression indexes are developed, which help to identify and handle cross-hybridizing probes and contaminating array regions.
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