Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2011-07-30
    Description: Head and neck squamous cell carcinoma (HNSCC) is a common, morbid, and frequently lethal malignancy. To uncover its mutational spectrum, we analyzed whole-exome sequencing data from 74 tumor-normal pairs. The majority exhibited a mutational profile consistent with tobacco exposure; human papillomavirus was detectable by sequencing DNA from infected tumors. In addition to identifying previously known HNSCC genes (TP53, CDKN2A, PTEN, PIK3CA, and HRAS), our analysis revealed many genes not previously implicated in this malignancy. At least 30% of cases harbored mutations in genes that regulate squamous differentiation (for example, NOTCH1, IRF6, and TP63), implicating its dysregulation as a major driver of HNSCC carcinogenesis. More generally, the results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415217/" 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/PMC3415217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stransky, Nicolas -- Egloff, Ann Marie -- Tward, Aaron D -- Kostic, Aleksandar D -- Cibulskis, Kristian -- Sivachenko, Andrey -- Kryukov, Gregory V -- Lawrence, Michael S -- Sougnez, Carrie -- McKenna, Aaron -- Shefler, Erica -- Ramos, Alex H -- Stojanov, Petar -- Carter, Scott L -- Voet, Douglas -- Cortes, Maria L -- Auclair, Daniel -- Berger, Michael F -- Saksena, Gordon -- Guiducci, Candace -- Onofrio, Robert C -- Parkin, Melissa -- Romkes, Marjorie -- Weissfeld, Joel L -- Seethala, Raja R -- Wang, Lin -- Rangel-Escareno, Claudia -- Fernandez-Lopez, Juan Carlos -- Hidalgo-Miranda, Alfredo -- Melendez-Zajgla, Jorge -- Winckler, Wendy -- Ardlie, Kristin -- Gabriel, Stacey B -- Meyerson, Matthew -- Lander, Eric S -- Getz, Gad -- Golub, Todd R -- Garraway, Levi A -- Grandis, Jennifer R -- P50 CA097190/CA/NCI NIH HHS/ -- R01 CA077308/CA/NCI NIH HHS/ -- R01 CA098372/CA/NCI NIH HHS/ -- UL1 TR000005/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 26;333(6046):1157-60. doi: 10.1126/science.1208130. Epub 2011 Jul 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21798893" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Apoptosis ; Carcinoma/*genetics/metabolism/virology ; Carcinoma, Squamous Cell ; Cell Differentiation ; Exons ; Head and Neck Neoplasms/*genetics/metabolism/virology ; Humans ; *Mutation ; Neoplasms, Squamous Cell/*genetics/metabolism/virology ; Papillomaviridae/isolation & purification ; Papillomavirus Infections/virology ; Point Mutation ; Receptor, Notch1/*genetics/metabolism ; *Sequence Analysis, DNA ; Sequence Deletion ; Signal Transduction ; Smoking ; Tobacco
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2014-01-07
    Description: Although a few cancer genes are mutated in a high proportion of tumours of a given type (〉20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600-5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048962/" 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/PMC4048962/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lawrence, Michael S -- Stojanov, Petar -- Mermel, Craig H -- Robinson, James T -- Garraway, Levi A -- Golub, Todd R -- Meyerson, Matthew -- Gabriel, Stacey B -- Lander, Eric S -- Getz, Gad -- R01 CA157304/CA/NCI NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 23;505(7484):495-501. doi: 10.1038/nature12912. Epub 2014 Jan 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Massachusetts General Hospital, Cancer Center and Department of Pathology, 55 Fruit Street, Boston, Massachusetts 02114, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [4] Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815, USA. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [3] Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA [4]. ; 1] Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA [2] Massachusetts General Hospital, Cancer Center and Department of Pathology, 55 Fruit Street, Boston, Massachusetts 02114, USA [3] Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [4].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24390350" target="_blank"〉PubMed〈/a〉
    Keywords: Apoptosis/genetics ; Case-Control Studies ; Cell Proliferation ; Chromatin/genetics ; DNA Mutational Analysis ; Exome/genetics ; Genes, Neoplasm/*genetics ; Genome, Human/genetics ; Genomic Instability/genetics ; Genomics ; Humans ; Immune Evasion/genetics ; Mutation Rate ; Neoplasms/*classification/*genetics/pathology ; Point Mutation/genetics ; RNA Processing, Post-Transcriptional/genetics ; Sample Size
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2012-03-31
    Description: The systematic translation of cancer genomic data into knowledge of tumour biology and therapeutic possibilities remains challenging. Such efforts should be greatly aided by robust preclinical model systems that reflect the genomic diversity of human cancers and for which detailed genetic and pharmacological annotation is available. Here we describe the Cancer Cell Line Encyclopedia (CCLE): a compilation of gene expression, chromosomal copy number and massively parallel sequencing data from 947 human cancer cell lines. When coupled with pharmacological profiles for 24 anticancer drugs across 479 of the cell lines, this collection allowed identification of genetic, lineage, and gene-expression-based predictors of drug sensitivity. In addition to known predictors, we found that plasma cell lineage correlated with sensitivity to IGF1 receptor inhibitors; AHR expression was associated with MEK inhibitor efficacy in NRAS-mutant lines; and SLFN11 expression predicted sensitivity to topoisomerase inhibitors. Together, our results indicate that large, annotated cell-line collections may help to enable preclinical stratification schemata for anticancer agents. The generation of genetic predictions of drug response in the preclinical setting and their incorporation into cancer clinical trial design could speed the emergence of 'personalized' therapeutic regimens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320027/" 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/PMC3320027/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Barretina, Jordi -- Caponigro, Giordano -- Stransky, Nicolas -- Venkatesan, Kavitha -- Margolin, Adam A -- Kim, Sungjoon -- Wilson, Christopher J -- Lehar, Joseph -- Kryukov, Gregory V -- Sonkin, Dmitriy -- Reddy, Anupama -- Liu, Manway -- Murray, Lauren -- Berger, Michael F -- Monahan, John E -- Morais, Paula -- Meltzer, Jodi -- Korejwa, Adam -- Jane-Valbuena, Judit -- Mapa, Felipa A -- Thibault, Joseph -- Bric-Furlong, Eva -- Raman, Pichai -- Shipway, Aaron -- Engels, Ingo H -- Cheng, Jill -- Yu, Guoying K -- Yu, Jianjun -- Aspesi, Peter Jr -- de Silva, Melanie -- Jagtap, Kalpana -- Jones, Michael D -- Wang, Li -- Hatton, Charles -- Palescandolo, Emanuele -- Gupta, Supriya -- Mahan, Scott -- Sougnez, Carrie -- Onofrio, Robert C -- Liefeld, Ted -- MacConaill, Laura -- Winckler, Wendy -- Reich, Michael -- Li, Nanxin -- Mesirov, Jill P -- Gabriel, Stacey B -- Getz, Gad -- Ardlie, Kristin -- Chan, Vivien -- Myer, Vic E -- Weber, Barbara L -- Porter, Jeff -- Warmuth, Markus -- Finan, Peter -- Harris, Jennifer L -- Meyerson, Matthew -- Golub, Todd R -- Morrissey, Michael P -- Sellers, William R -- Schlegel, Robert -- Garraway, Levi A -- DP2 OD002750/OD/NIH HHS/ -- DP2 OD002750-01/OD/NIH HHS/ -- R33 CA126674/CA/NCI NIH HHS/ -- R33 CA126674-04/CA/NCI NIH HHS/ -- R33 CA155554/CA/NCI NIH HHS/ -- R33 CA155554-02/CA/NCI NIH HHS/ -- England -- Nature. 2012 Mar 28;483(7391):603-7. doi: 10.1038/nature11003.〈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/22460905" target="_blank"〉PubMed〈/a〉
    Keywords: Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Lineage ; Chromosomes, Human/genetics ; Clinical Trials as Topic/methods ; *Databases, Factual ; Drug Screening Assays, Antitumor/*methods ; *Encyclopedias as Topic ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Genes, ras/genetics ; Genome, Human/genetics ; Genomics ; Humans ; Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/metabolism ; *Models, Biological ; Neoplasms/*drug therapy/genetics/metabolism/*pathology ; Pharmacogenetics ; Plasma Cells/cytology/drug effects/metabolism ; Precision Medicine/methods ; Receptor, IGF Type 1/antagonists & inhibitors/metabolism ; Receptors, Aryl Hydrocarbon/genetics/metabolism ; Sequence Analysis, DNA ; Topoisomerase Inhibitors/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2014-01-07
    Description: Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations in the pathogenesis of cervical carcinomas. Here we report whole-exome sequencing analysis of 115 cervical carcinoma-normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour-normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4161954/" 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/PMC4161954/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ojesina, Akinyemi I -- Lichtenstein, Lee -- Freeman, Samuel S -- Pedamallu, Chandra Sekhar -- Imaz-Rosshandler, Ivan -- Pugh, Trevor J -- Cherniack, Andrew D -- Ambrogio, Lauren -- Cibulskis, Kristian -- Bertelsen, Bjorn -- Romero-Cordoba, Sandra -- Trevino, Victor -- Vazquez-Santillan, Karla -- Guadarrama, Alberto Salido -- Wright, Alexi A -- Rosenberg, Mara W -- Duke, Fujiko -- Kaplan, Bethany -- Wang, Rui -- Nickerson, Elizabeth -- Walline, Heather M -- Lawrence, Michael S -- Stewart, Chip -- Carter, Scott L -- McKenna, Aaron -- Rodriguez-Sanchez, Iram P -- Espinosa-Castilla, Magali -- Woie, Kathrine -- Bjorge, Line -- Wik, Elisabeth -- Halle, Mari K -- Hoivik, Erling A -- Krakstad, Camilla -- Gabino, Nayeli Belem -- Gomez-Macias, Gabriela Sofia -- Valdez-Chapa, Lezmes D -- Garza-Rodriguez, Maria Lourdes -- Maytorena, German -- Vazquez, Jorge -- Rodea, Carlos -- Cravioto, Adrian -- Cortes, Maria L -- Greulich, Heidi -- Crum, Christopher P -- Neuberg, Donna S -- Hidalgo-Miranda, Alfredo -- Escareno, Claudia Rangel -- Akslen, Lars A -- Carey, Thomas E -- Vintermyr, Olav K -- Gabriel, Stacey B -- Barrera-Saldana, Hugo A -- Melendez-Zajgla, Jorge -- Getz, Gad -- Salvesen, Helga B -- Meyerson, Matthew -- K07 CA166210/CA/NCI NIH HHS/ -- T32 CA009676/CA/NCI NIH HHS/ -- England -- Nature. 2014 Feb 20;506(7488):371-5. doi: 10.1038/nature12881. Epub 2013 Dec 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [3]. ; 1] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [2]. ; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. ; Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico. ; Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway. ; Tecnologico de Monterrey, Monterrey 64849, Mexico. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China. ; Cancer Biology Program, Program in the Biomedical Sciences, Rackham Graduate School, University of Michigan, Ann Arbor, Michigan 48109, USA. ; Facultad de Medicina y Hospital Universitario 'Dr. Jose Eluterio Gonzalez' de la Universidad Autonoma de Nuevo Leon, Monterrey, Nuevo Leon 64460, Mexico. ; Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway. ; 1] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway. ; Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [3] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. ; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. ; 1] Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico [2] Claremont Graduate University, Claremont, California 91711, USA. ; 1] Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway [2] Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, N5020 Bergen, Norway. ; Head and Neck Oncology Program and Department of Otolaryngology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 38109, USA. ; 1] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [2] Massachusetts General Hospital Cancer Center and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. ; 1] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway [3]. ; 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [3] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [4].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24390348" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/genetics/virology ; Carcinoma, Squamous Cell/genetics/virology ; Case-Control Studies ; Cell Cycle Proteins/genetics ; Core Binding Factor beta Subunit/genetics ; DNA Copy Number Variations/genetics ; DNA Mutational Analysis ; DNA-Binding Proteins/genetics ; E1A-Associated p300 Protein/genetics ; Exome/genetics ; F-Box Proteins/genetics ; Female ; Gene Expression Regulation, Neoplastic/genetics ; Genome, Human/*genetics ; Genomics ; HLA-B Antigens/genetics ; Humans ; Mitogen-Activated Protein Kinase 1/genetics ; Mutation/*genetics ; NF-E2-Related Factor 2/genetics ; Papillomaviridae/genetics/physiology ; Papillomavirus Infections/genetics ; Proto-Oncogene Proteins/genetics ; Proto-Oncogene Proteins c-ets ; Receptor, ErbB-2/genetics ; Transcription Factors/genetics ; Transcriptome/genetics ; Tumor Suppressor Protein p53/genetics ; Ubiquitin-Protein Ligases/genetics ; Uterine Cervical Neoplasms/*genetics/virology ; Virus Integration/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2011-03-25
    Description: Multiple myeloma is an incurable malignancy of plasma cells, and its pathogenesis is poorly understood. Here we report the massively parallel sequencing of 38 tumour genomes and their comparison to matched normal DNAs. Several new and unexpected oncogenic mechanisms were suggested by the pattern of somatic mutation across the data set. These include the mutation of genes involved in protein translation (seen in nearly half of the patients), genes involved in histone methylation, and genes involved in blood coagulation. In addition, a broader than anticipated role of NF-kappaB signalling was indicated by mutations in 11 members of the NF-kappaB pathway. Of potential immediate clinical relevance, activating mutations of the kinase BRAF were observed in 4% of patients, suggesting the evaluation of BRAF inhibitors in multiple myeloma clinical trials. These results indicate that cancer genome sequencing of large collections of samples will yield new insights into cancer not anticipated by existing knowledge.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560292/" 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/PMC3560292/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chapman, Michael A -- Lawrence, Michael S -- Keats, Jonathan J -- Cibulskis, Kristian -- Sougnez, Carrie -- Schinzel, Anna C -- Harview, Christina L -- Brunet, Jean-Philippe -- Ahmann, Gregory J -- Adli, Mazhar -- Anderson, Kenneth C -- Ardlie, Kristin G -- Auclair, Daniel -- Baker, Angela -- Bergsagel, P Leif -- Bernstein, Bradley E -- Drier, Yotam -- Fonseca, Rafael -- Gabriel, Stacey B -- Hofmeister, Craig C -- Jagannath, Sundar -- Jakubowiak, Andrzej J -- Krishnan, Amrita -- Levy, Joan -- Liefeld, Ted -- Lonial, Sagar -- Mahan, Scott -- Mfuko, Bunmi -- Monti, Stefano -- Perkins, Louise M -- Onofrio, Robb -- Pugh, Trevor J -- Rajkumar, S Vincent -- Ramos, Alex H -- Siegel, David S -- Sivachenko, Andrey -- Stewart, A Keith -- Trudel, Suzanne -- Vij, Ravi -- Voet, Douglas -- Winckler, Wendy -- Zimmerman, Todd -- Carpten, John -- Trent, Jeff -- Hahn, William C -- Garraway, Levi A -- Meyerson, Matthew -- Lander, Eric S -- Getz, Gad -- Golub, Todd R -- K12 CA133250/CA/NCI NIH HHS/ -- R01 AG020686/AG/NIA NIH HHS/ -- R01 AG020686-07/AG/NIA NIH HHS/ -- R01 CA133115/CA/NCI NIH HHS/ -- R01 CA133115-04/CA/NCI NIH HHS/ -- R01 CA133966/CA/NCI NIH HHS/ -- R01 CA133966-03/CA/NCI NIH HHS/ -- England -- Nature. 2011 Mar 24;471(7339):467-72. doi: 10.1038/nature09837.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Eli and Edythe L. Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02412, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430775" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Blood Coagulation/genetics ; CpG Islands/genetics ; DNA Mutational Analysis ; DNA Repair/genetics ; Exons/genetics ; Exosome Multienzyme Ribonuclease Complex ; Genome, Human/*genetics ; Genomics ; Histones/metabolism ; Homeodomain Proteins/genetics ; Homeostasis/genetics ; Humans ; Methylation ; Models, Molecular ; Molecular Sequence Data ; Multiple Myeloma/drug therapy/enzymology/*genetics/metabolism ; Mutation/*genetics ; NF-kappa B/metabolism ; Oncogenes/genetics ; Open Reading Frames/genetics ; Protein Biosynthesis/genetics ; Protein Conformation ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors/genetics/metabolism ; RNA Processing, Post-Transcriptional/genetics ; Ribonucleases/chemistry/genetics ; Signal Transduction/genetics ; Transcription, Genetic/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2012-06-23
    Description: Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy. Recurrent somatic alterations in breast cancer have been described, including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration. Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements. Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA, TP53, AKT1, GATA3 and MAP3K1, we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression. The MAGI3-AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4148686/" 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/PMC4148686/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Banerji, Shantanu -- Cibulskis, Kristian -- Rangel-Escareno, Claudia -- Brown, Kristin K -- Carter, Scott L -- Frederick, Abbie M -- Lawrence, Michael S -- Sivachenko, Andrey Y -- Sougnez, Carrie -- Zou, Lihua -- Cortes, Maria L -- Fernandez-Lopez, Juan C -- Peng, Shouyong -- Ardlie, Kristin G -- Auclair, Daniel -- Bautista-Pina, Veronica -- Duke, Fujiko -- Francis, Joshua -- Jung, Joonil -- Maffuz-Aziz, Antonio -- Onofrio, Robert C -- Parkin, Melissa -- Pho, Nam H -- Quintanar-Jurado, Valeria -- Ramos, Alex H -- Rebollar-Vega, Rosa -- Rodriguez-Cuevas, Sergio -- Romero-Cordoba, Sandra L -- Schumacher, Steven E -- Stransky, Nicolas -- Thompson, Kristin M -- Uribe-Figueroa, Laura -- Baselga, Jose -- Beroukhim, Rameen -- Polyak, Kornelia -- Sgroi, Dennis C -- Richardson, Andrea L -- Jimenez-Sanchez, Gerardo -- Lander, Eric S -- Gabriel, Stacey B -- Garraway, Levi A -- Golub, Todd R -- Melendez-Zajgla, Jorge -- Toker, Alex -- Getz, Gad -- Hidalgo-Miranda, Alfredo -- Meyerson, Matthew -- CA089393/CA/NCI NIH HHS/ -- CA122099/CA/NCI NIH HHS/ -- R01 CA122099/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2012 Jun 20;486(7403):405-9. doi: 10.1038/nature11154.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722202" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Breast Neoplasms/*classification/*genetics/pathology ; Core Binding Factor Alpha 2 Subunit/genetics ; Core Binding Factor beta Subunit/genetics ; DNA Mutational Analysis ; Exome/genetics ; Female ; Gene Fusion/genetics ; Humans ; Membrane Proteins/genetics ; Mexico ; Mutation/*genetics ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors/genetics/metabolism ; Translocation, Genetic/*genetics ; Vietnam
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...