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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Genomic alterations in lung adenocarcinoma
TL;DR: Sequencing data from large-scale consortia, such as The Cancer Genome Atlas, as well as several independent groups, have helped identify novel drivers and potentially targetable alterations in lung adenocarcinomas.
Journal ArticleDOI
Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2+ breast cancer patients
Maurizio Scaltriti,Pieter Johan Adam Eichhorn,Javier Cortes,Ludmila Prudkin,Claudia Aura,Jose Jimenez,Sarat Chandarlapaty,Violeta Serra,Aleix Prat,Yasir H. Ibrahim,Marta Guzman,Magui Gili,Olga Graciela Cantu Rodriguez,Sonia Rodríguez,José Francisco Pérez,Simon Green,Sabine Mai,Neal Rosen,Clifford A. Hudis,José Baselga +19 more
TL;DR: The findings point to a causative role for cyclin E overexpression and the consequent increase inCDK2 activity in trastuzumab resistance and suggest that treatment with CDK2 inhibitors may be a valid strategy in patients with breast tumors with HER2 and Cyclin E coamplification/overexpression.
Journal ArticleDOI
Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor
J. Keith Killian,Su Young Kim,Markku Miettinen,Carly J Smith,Maria J. Merino,Maria Tsokos,Martha Quezado,William I. Smith,Mona S. Jahromi,Paraskevi Xekouki,Eva Szarek,Robert L. Walker,Jerzy Lasota,Mark Raffeld,Brandy Klotzle,Zengfeng Wang,Laura Jones,Yuelin Zhu,Yonghong Wang,Joshua J. Waterfall,Maureen J. O'Sullivan,Marina Bibikova,Karel Pacak,Constantine A. Stratakis,Katherine A. Janeway,Joshua D. Schiffman,Jian-Bing Fan,Lee J. Helman,Paul S. Meltzer +28 more
TL;DR: A striking divergence is uncovered between the DNA methylation profiles of SDH-deficient GIST versus KIT tyrosine kinase pathway-mutated GIST, which generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.
Journal ArticleDOI
Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers
Xiaoyang Zhang,Peter S. Choi,Peter S. Choi,Joshua M. Francis,Joshua M. Francis,Marcin Imielinski,Marcin Imielinski,Hideo Watanabe,Andrew D. Cherniack,Matthew Meyerson +9 more
TL;DR: The results suggest that genomic amplification of super-enhancers represents a common mechanism to activate cancer driver genes in multiple cancer types.
Journal ArticleDOI
Targeting the eIF4F translation initiation complex: a critical nexus for cancer development.
TL;DR: Identification of mRNAs particularly responsive to elevated eIF4F activity that typifies tumorigenesis underscores the critical role of eif4F in cancer and raises the exciting possibility of developing new-in-class small molecules targeting translation initiation as antineoplastic agents.
References
More filters
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.
Related Papers (5)
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Tilman Oltersdorf,Steven W. Elmore,Alexander R. Shoemaker,Robert C. Armstrong,David J. Augeri,Barbara A. Belli,Milan Bruncko,Thomas L. Deckwerth,Jürgen Dinges,Philip J. Hajduk,Mary K. Joseph,Shinichi Kitada,Stanley J. Korsmeyer,Stanley J. Korsmeyer,Kunzer Aaron R,Anthony Letai,Chi Li,Michael J. Mitten,David G. Nettesheim,Shi Chung Ng,Paul Nimmer,Jacqueline M. O'Connor,Anatol Oleksijew,Andrew M. Petros,John C. Reed,Wang Shen,Stephen K. Tahir,Craig B. Thompson,Kevin J. Tomaselli,Baole Wang,Wendt Michael D,Haichao Zhang,Stephen W. Fesik,Saul H. Rosenberg +33 more
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