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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Insulin-Like Growth Factor (IGF) Pathway Targeting in Cancer: Role of the IGF Axis and Opportunities for Future Combination Studies.
Aaron D. Simpson,Wilfride Petnga,Valentine M. Macaulay,Ulrike Weyer-Czernilofsky,Thomas Bogenrieder,Thomas Bogenrieder +5 more
TL;DR: The preclinical and clinical experience with IGF-targeted therapies to-date are reviewed, and the rationale for future combination approaches as a means to overcome treatment resistance is discussed.
Journal ArticleDOI
An analysis of genetic heterogeneity in untreated cancers.
Johannes G. Reiter,Marina Baretti,Jeffrey M. Gerold,Alvin Makohon-Moore,Adil Daud,Christine A. Iacobuzio-Donahue,Nilofer S. Azad,Kenneth W. Kinzler,Martin A. Nowak,Bert Vogelstein +9 more
TL;DR: The analyses indicate that the cells within the primary tumours that gave rise to metastases are genetically homogeneous with respect to functional driver-gene mutations, and it is suggested that future efforts to develop combination therapies have the potential to be curative.
Journal ArticleDOI
MCL-1 is a prognostic indicator and drug target in breast cancer.
Kirsteen J. Campbell,Sandeep Dhayade,Nicola Ferrari,Andrew H. Sims,Emma Johnson,Susan M. Mason,Ashley Dickson,Kevin M. Ryan,Gabriela Kalna,Joanne Edwards,Stephen W.G. Tait,Karen Blyth +11 more
TL;DR: In this article, the authors investigated MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data, finding that high MCL1 expression is associated with poor outcome in breast cancer.
Journal ArticleDOI
Mcl-1 promotes lung cancer cell migration by directly interacting with VDAC to increase mitochondrial Ca2+ uptake and reactive oxygen species generation.
TL;DR: The physiological significance of an interaction between Mcl-1 and the mitochondrial outer membrane-localized voltage-dependent anion channel (VDAC) in NSCLC cell lines is reported and it is suggested that an interaction Between Mcl1 and VDAC promotes lung cancer cell migration by a mechanism that involves Ca2-dependent ROS production.
Journal ArticleDOI
Intracellular localization of the BCL-2 family member BOK and functional implications
Nohemy Echeverry,Daniel Bachmann,Francine Ke,Francine Ke,Andreas Strasser,Andreas Strasser,Hans-Uwe Simon,Thomas Kaufmann +7 more
TL;DR: It is proposed that major functions of BOK are exerted at the Golgi and ER membranes and that BOK induces apoptosis in a manner dependent on BAX and BAK.
References
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Journal ArticleDOI
Controlling the false discovery rate: a practical and powerful approach to multiple testing
Yoav Benjamini,Yosef Hochberg +1 more
TL;DR: In this paper, a different approach to problems of multiple significance testing is presented, which calls for controlling the expected proportion of falsely rejected hypotheses -the false discovery rate, which is equivalent to the FWER when all hypotheses are true but is smaller otherwise.
Journal ArticleDOI
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
Roger E. McLendon,Allan H. Friedman,Darrell D. Bigner,Erwin G. Van Meir,Daniel J. Brat,Gena M. Mastrogianakis,Jeffrey J. Olson,Tom Mikkelsen,Norman L. Lehman,Kenneth Aldape,W. K. Alfred Yung,Oliver Bogler,John N. Weinstein,Scott R. VandenBerg,Mitchel S. Berger,Michael D. Prados,Donna M. Muzny,Margaret Morgan,Steve Scherer,Aniko Sabo,Lynn Nazareth,Lora Lewis,Otis Hall,Yiming Zhu,Yanru Ren,Omar Alvi,Jiqiang Yao,Alicia Hawes,Shalini N. Jhangiani,Gerald R. Fowler,Anthony San Lucas,Christie Kovar,Andrew Cree,Huyen Dinh,Jireh Santibanez,Vandita Joshi,Manuel L. Gonzalez-Garay,Christopher A. Miller,Aleksandar Milosavljevic,Lawrence A. Donehower,David A. Wheeler,Richard A. Gibbs,Kristian Cibulskis,Carrie Sougnez,Timothy Fennell,Scott Mahan,Jane Wilkinson,Liuda Ziaugra,Robert C. Onofrio,Toby Bloom,Rob Nicol,Kristin G. Ardlie,Jennifer Baldwin,Stacey Gabriel,Eric S. Lander,Eric S. Lander,Li Ding,Robert S. Fulton,Michael D. McLellan,John W. Wallis,David E. Larson,Xiaoqi Shi,Rachel Abbott,Lucinda Fulton,Ken Chen,Daniel C. Koboldt,Michael C. Wendl,Rick Meyer,Yuzhu Tang,Ling Lin,John R. Osborne,Brian H. Dunford-Shore,Tracie L. Miner,Kim D. Delehaunty,Chris Markovic,Gary W. Swift,William Courtney,Craig Pohl,Scott Abbott,Amy Hawkins,Shin Leong,Carrie A. Haipek,Heather Schmidt,Maddy Wiechert,Tammi L. Vickery,Sacha Scott,David J. Dooling,Asif T. Chinwalla,George M. Weinstock,Elaine R. Mardis,Richard K. Wilson,Gad Getz,Wendy Winckler,Roel G.W. Verhaak,Michael S. Lawrence,Michael J. T. O’Kelly,James A. Robinson,Gabriele Alexe,Rameen Beroukhim,Scott L. Carter,Derek Y. Chiang,Josh Gould,Supriya Gupta,Josh Korn,Craig H. Mermel,Jill P. Mesirov,Stefano Monti,Huy V. Nguyen,Melissa Parkin,Michael R. Reich,Nicolas Stransky,Barbara A. Weir,Levi A. Garraway,Todd R. Golub,Matthew Meyerson,Lynda Chin,Alexei Protopopov,Jianhua Zhang,Ilana Perna,Sandy Aronson,Narayanan Sathiamoorthy,Georgia Ren,Jun Yao,W. Ruprecht Wiedemeyer,Hyun Soo Kim,Won Kong Sek,Yonghong Xiao,Isaac S. Kohane,Jon G. Seidman,Peter J. Park,Raju Kucherlapati,Peter W. Laird,Leslie Cope,James G. Herman,Daniel J. Weisenberger,Fei Pan,David Van Den Berg,Leander Van Neste,Mi Yi Joo,Kornel E. Schuebel,Stephen B. Baylin,Devin Absher,Jun Li,Audrey Southwick,Shannon T. Brady,Amita Aggarwal,Tisha Chung,Gavin Sherlock,James D. Brooks,Richard M. Myers,Paul T. Spellman,Elizabeth Purdom,Lakshmi Jakkula,Anna Lapuk,Henry Marr,Shannon Dorton,Gi Choi Yoon,Ju Han,Amrita Ray,Victoria Wang,Steffen Durinck,Mark D. Robinson,Nicholas J. Wang,Karen Vranizan,Vivian Peng,Eric Van Name,Gerald V. Fontenay,John Ngai,John G. Conboy,Bahram Parvin,Heidi S. Feiler,Terence P. Speed,Terence P. Speed,Joe W. Gray,Cameron Brennan,Nicholas D. Socci,Adam B. Olshen,Barry S. Taylor,Barry S. Taylor,Alex E. Lash,Nikolaus Schultz,Boris Reva,Yevgeniy Antipin,Alexey Stukalov,Benjamin Gross,Ethan Cerami,Qing Wang Wei,Li-Xuan Qin,Venkatraman E. Seshan,Liliana Villafania,Magali Cavatore,Laetitia Borsu,Agnes Viale,William L. Gerald,Chris Sander,Marc Ladanyi,Charles M. Perou,D. Neil Hayes,Michael D. Topal,Katherine A. Hoadley,Yuan Qi,Sai Balu,Yan Shi,Junyuan Wu,Robert Penny,Michael L. Bittner,Troy Shelton,Elizabeth Lenkiewicz,Scott Morris,Debbie Beasley,Sheri Sanders,Ari B. Kahn,Robert Sfeir,Jessica Chen,David Nassau,Larry Feng,Erin Hickey,Anna D. Barker,Daniela S. Gerhard,Joseph G. Vockley,Carolyn C. Compton,Jim Vaught,Peter Fielding,Martin L. Ferguson,Carl F. Schaefer,Jinghui Zhang,Subhashree Madhavan,Kenneth H. Buetow,Francis S. Collins,Peter J. Good,Mark S. Guyer,Brad Ozenberger,Jane Peterson,Elizabeth J. Thomson +233 more
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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