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  • 1
    Publication Date: 2011-02-11
    Description: Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, 'copy-neutral') rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2-ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075885/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3075885/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berger, Michael F -- Lawrence, Michael S -- Demichelis, Francesca -- Drier, Yotam -- Cibulskis, Kristian -- Sivachenko, Andrey Y -- Sboner, Andrea -- Esgueva, Raquel -- Pflueger, Dorothee -- Sougnez, Carrie -- Onofrio, Robert -- Carter, Scott L -- Park, Kyung -- Habegger, Lukas -- Ambrogio, Lauren -- Fennell, Timothy -- Parkin, Melissa -- Saksena, Gordon -- Voet, Douglas -- Ramos, Alex H -- Pugh, Trevor J -- Wilkinson, Jane -- Fisher, Sheila -- Winckler, Wendy -- Mahan, Scott -- Ardlie, Kristin -- Baldwin, Jennifer -- Simons, Jonathan W -- Kitabayashi, Naoki -- MacDonald, Theresa Y -- Kantoff, Philip W -- Chin, Lynda -- Gabriel, Stacey B -- Gerstein, Mark B -- Golub, Todd R -- Meyerson, Matthew -- Tewari, Ashutosh -- Lander, Eric S -- Getz, Gad -- Rubin, Mark A -- Garraway, Levi A -- 2 P50 CA090381-11/CA/NCI NIH HHS/ -- DP2 OD002750/OD/NIH HHS/ -- DP2 OD002750-01/OD/NIH HHS/ -- R33 CA126674/CA/NCI NIH HHS/ -- R33 CA126674-03/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Feb 10;470(7333):214-20. doi: 10.1038/nature09744.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21307934" target="_blank"〉PubMed〈/a〉
    Keywords: Carrier Proteins/genetics ; Case-Control Studies ; Cell Adhesion Molecules/genetics ; Chromatin/genetics/metabolism ; Chromosome Aberrations ; Chromosome Breakpoints ; Epigenesis, Genetic/genetics ; Gene Expression Regulation, Neoplastic ; Genome, Human/*genetics ; Humans ; Male ; PTEN Phosphohydrolase/genetics/metabolism ; Prostatic Neoplasms/*genetics ; Recombination, Genetic/genetics ; Signal Transduction/genetics ; Transcription, Genetic
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-12-24
    Description: We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor-binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor-binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142569/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142569/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gerstein, Mark B -- Lu, Zhi John -- Van Nostrand, Eric L -- Cheng, Chao -- Arshinoff, Bradley I -- Liu, Tao -- Yip, Kevin Y -- Robilotto, Rebecca -- Rechtsteiner, Andreas -- Ikegami, Kohta -- Alves, Pedro -- Chateigner, Aurelien -- Perry, Marc -- Morris, Mitzi -- Auerbach, Raymond K -- Feng, Xin -- Leng, Jing -- Vielle, Anne -- Niu, Wei -- Rhrissorrakrai, Kahn -- Agarwal, Ashish -- Alexander, Roger P -- Barber, Galt -- Brdlik, Cathleen M -- Brennan, Jennifer -- Brouillet, Jeremy Jean -- Carr, Adrian -- Cheung, Ming-Sin -- Clawson, Hiram -- Contrino, Sergio -- Dannenberg, Luke O -- Dernburg, Abby F -- Desai, Arshad -- Dick, Lindsay -- Dose, Andrea C -- Du, Jiang -- Egelhofer, Thea -- Ercan, Sevinc -- Euskirchen, Ghia -- Ewing, Brent -- Feingold, Elise A -- Gassmann, Reto -- Good, Peter J -- Green, Phil -- Gullier, Francois -- Gutwein, Michelle -- Guyer, Mark S -- Habegger, Lukas -- Han, Ting -- Henikoff, Jorja G -- Henz, Stefan R -- Hinrichs, Angie -- Holster, Heather -- Hyman, Tony -- Iniguez, A Leo -- Janette, Judith -- Jensen, Morten -- Kato, Masaomi -- Kent, W James -- Kephart, Ellen -- Khivansara, Vishal -- Khurana, Ekta -- Kim, John K -- Kolasinska-Zwierz, Paulina -- Lai, Eric C -- Latorre, Isabel -- Leahey, Amber -- Lewis, Suzanna -- Lloyd, Paul -- Lochovsky, Lucas -- Lowdon, Rebecca F -- Lubling, Yaniv -- Lyne, Rachel -- MacCoss, Michael -- Mackowiak, Sebastian D -- Mangone, Marco -- McKay, Sheldon -- Mecenas, Desirea -- Merrihew, Gennifer -- Miller, David M 3rd -- Muroyama, Andrew -- Murray, John I -- Ooi, Siew-Loon -- Pham, Hoang -- Phippen, Taryn -- Preston, Elicia A -- Rajewsky, Nikolaus -- Ratsch, Gunnar -- Rosenbaum, Heidi -- Rozowsky, Joel -- Rutherford, Kim -- Ruzanov, Peter -- Sarov, Mihail -- Sasidharan, Rajkumar -- Sboner, Andrea -- Scheid, Paul -- Segal, Eran -- Shin, Hyunjin -- Shou, Chong -- Slack, Frank J -- Slightam, Cindie -- Smith, Richard -- Spencer, William C -- Stinson, E O -- Taing, Scott -- Takasaki, Teruaki -- Vafeados, Dionne -- Voronina, Ksenia -- Wang, Guilin -- Washington, Nicole L -- Whittle, Christina M -- Wu, Beijing -- Yan, Koon-Kiu -- Zeller, Georg -- Zha, Zheng -- Zhong, Mei -- Zhou, Xingliang -- modENCODE Consortium -- Ahringer, Julie -- Strome, Susan -- Gunsalus, Kristin C -- Micklem, Gos -- Liu, X Shirley -- Reinke, Valerie -- Kim, Stuart K -- Hillier, LaDeana W -- Henikoff, Steven -- Piano, Fabio -- Snyder, Michael -- Stein, Lincoln -- Lieb, Jason D -- Waterston, Robert H -- 054523/Wellcome Trust/United Kingdom -- R01 GM088565/GM/NIGMS NIH HHS/ -- R01 GM088565-03/GM/NIGMS NIH HHS/ -- R01GM088565/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Dec 24;330(6012):1775-87. doi: 10.1126/science.1196914. Epub 2010 Dec 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Computational Biology and Bioinformatics, Yale University, Bass 432, 266 Whitney Avenue, New Haven, CT 06520, USA. modencode.worm.pi@gersteinlab.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21177976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*genetics/growth & development/metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; Chromatin/genetics/metabolism/ultrastructure ; *Chromosomes/genetics/metabolism/ultrastructure ; Computational Biology/methods ; Conserved Sequence ; Evolution, Molecular ; *Gene Expression Profiling ; *Gene Expression Regulation ; Gene Regulatory Networks ; Genes, Helminth ; *Genome, Helminth ; Genomics/methods ; Histones/metabolism ; Models, Genetic ; *Molecular Sequence Annotation ; RNA, Helminth/genetics/metabolism ; RNA, Untranslated/genetics/metabolism ; Regulatory Sequences, Nucleic Acid ; Transcription Factors/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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