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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A genetic basis for the variation in the vulnerability of cancer to DNA damage
B. Yard,Drew J. Adams,Eui Kyu Chie,Eui Kyu Chie,Pablo Tamayo,Jessica S. Battaglia,Priyanka Gopal,Kevin Rogacki,Bradley E. Pearson,James G. Phillips,Daniel P. Raymond,Nathan A. Pennell,Francisco A. Almeida,Jaime H. Cheah,Paul A. Clemons,Alykhan F. Shamji,Craig D. Peacock,Stuart L. Schreiber,Stuart L. Schreiber,Stuart L. Schreiber,Peter S. Hammerman,Peter S. Hammerman,Mohamed E. Abazeed +22 more
TL;DR: Large-scale profiling of cellular survival after exposure to radiation in a diverse collection of 533 genetically annotated human tumour cell lines shows that sensitivity to radiation is characterized by significant variation across and within lineages.
Journal ArticleDOI
Amplification and high-level expression of heat shock protein 90 marks aggressive phenotypes of human epidermal growth factor receptor 2 negative breast cancer
Qing Cheng,Jeffrey T. Chang,Joseph Geradts,Leonard M. Neckers,Timothy A.J. Haystead,Neil L. Spector,H. Kim Lyerly +6 more
TL;DR: Up-regulated HSP90 mRNA expression represents a confluence of genomic vulnerability that renders HER2 negative breast cancers more aggressive, resulting in poor prognosis, and Targeting breast cancer with up-regulatedHSP90 may potentially improve the effectiveness of clinical intervention in this disease.
Journal ArticleDOI
Evolution of the cancer genome
TL;DR: How cancer genomes are beginning to be investigated from an evolutionary perspective is outlined, recent progress in the cataloging of somatic genetic and genomic alterations is described, and the contributions of germline as well as epigenetic factors to cancer genome evolution are investigated.
Journal ArticleDOI
Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.
Laura M. Sack,Teresa Davoli,Mamie Z. Li,Yuyang Li,Qikai Xu,Kamila Naxerova,Eric C. Wooten,Ronald J. Bernardi,Timothy D. Martin,Ting Chen,Yumei Leng,Anthony C. Liang,Kathleen A. Scorsone,Thomas F. Westbrook,Kwok-Kin Wong,Kwok-Kin Wong,Stephen J. Elledge +16 more
TL;DR: A substantial contribution is reported to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and insights are derived about the genetic network architecture of aneuploidy in tumors.
Journal ArticleDOI
A cluster of cooperating tumor-suppressor gene candidates in chromosomal deletions
Wen Xue,Thomas Kitzing,Stephanie Roessler,Johannes Zuber,Alexander Krasnitz,Nikolaus Schultz,Kate Revill,Susann Weissmueller,Amy R. Rappaport,Janelle Simon,Jack Zhang,Weijun Luo,James W. Hicks,Lars Zender,Xin Wei Wang,Scott Powers,Michael Wigler,Scott W. Lowe +17 more
TL;DR: The data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events.
References
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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.
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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.
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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.
Journal ArticleDOI
Model-based analysis of oligonucleotide arrays: Expression index computation and outlier detection
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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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