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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Pan-cancer analysis of homozygous deletions in primary tumours uncovers rare tumour suppressors.
Jiqiu Cheng,Jiqiu Cheng,Jonas Demeulemeester,Jonas Demeulemeester,David C. Wedge,David C. Wedge,Hans Kristian Moen Vollan,Hans Kristian Moen Vollan,Jason J. Pitt,Hege G. Russnes,Bina P. Pandey,Gro Nilsen,Silje Nord,Graham R. Bignell,Kevin P. White,Anne Lise Børresen-Dale,Peter J. Campbell,Vessela N. Kristensen,Michael R. Stratton,Ole Christian Lingjærde,Yves Moreau,Peter Van Loo,Peter Van Loo +22 more
TL;DR: This study builds a compendium of 2218 primary tumours across 12 human cancer types and systematically screen for homozygous deletions and proposes 27 candidate tumour suppressors, including MAFTRR, KIAA1551, and IGF2BP2.
Journal ArticleDOI
Loss of the tyrosine phosphatase PTPRD leads to aberrant STAT3 activation and promotes gliomagenesis
Berenice Ortiz,Armida W. M. Fabius,Wei H. Wu,Alicia Pedraza,Cameron Brennan,Nikolaus Schultz,Kenneth L. Pitter,Jacqueline Bromberg,Jason T. Huse,Eric C. Holland,Timothy A. Chan +10 more
TL;DR: It is demonstrated that loss of Ptprd accelerates tumor formation and defined the oncogenic context in which PtPRd loss acts, and it is established that in human GBMs, heterozygous loss of PTPRD is the predominant type of lesion and that losses ofPTPRD and the CDKN2A/p16INK4A tumor suppressor frequently co-occur.
Journal ArticleDOI
Bif-1 haploinsufficiency promotes chromosomal instability and accelerates Myc-driven lymphomagenesis via suppression of mitophagy.
Yoshinori Takahashi,Tsukasa Hori,Timothy K. Cooper,Jason Liao,Neelam Desai,Jacob M. Serfass,Megan M. Young,Sungman Park,Yayoi Izu,Hong Gang Wang +9 more
TL;DR: It is reported that Bif-1 (Sh3glb1) is a haploinsufficiency tumor suppressor that plays a key role in the prevention of chromosomal instability and suppresses the acquisition of apoptosis resistance during Myc-driven lymphomagenesis.
Journal ArticleDOI
Focal aberrations indicate EYA2 and hsa‐miR‐375 as oncogene and tumor suppressor in cervical carcinogenesis
Mariska Bierkens,Oscar Krijgsman,Saskia M. Wilting,Leontien Bosch,Annelieke Jaspers,Gerrit A. Meijer,Chris J.L.M. Meijer,Peter J.F. Snijders,Bauke Ylstra,Renske D.M. Steenbergen +9 more
TL;DR: The data provide a proof of concept that chromosomal aberrations are actively contributing to HPV‐induced carcinogenesis and identify EYA2 and hsa‐miR‐375 as oncogene and tumor suppressor gene, respectively.
Journal ArticleDOI
Molecular and translational advances in meningiomas.
Suganth Suppiah,Farshad Nassiri,Wenya Linda Bi,Ian F. Dunn,Clemens Oliver Hanemann,Craig Horbinski,Rintaro Hashizume,Charles David James,Christian Mawrin,Houtan Noushmehr,Arie Perry,Felix Sahm,Andrew E. Sloan,Andreas von Deimling,Patrick Y. Wen,Kenneth Aldape,Gelareh Zadeh +16 more
TL;DR: The most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation are reviewed, and the landscape of available preclinical models in meningingiomas is highlighted.
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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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