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  1. Article ; Online: Oxytetracycline biosynthesis.

    Pickens, Lauren B / Tang, Yi

    The Journal of biological chemistry

    2010  Volume 285, Issue 36, Page(s) 27509–27515

    Abstract: Oxytetracycline (OTC) is a broad-spectrum antibiotic that acts by inhibiting protein synthesis in bacteria. It is an important member of the bacterial aromatic polyketide family, which is a structurally diverse class of natural products. OTC is ... ...

    Abstract Oxytetracycline (OTC) is a broad-spectrum antibiotic that acts by inhibiting protein synthesis in bacteria. It is an important member of the bacterial aromatic polyketide family, which is a structurally diverse class of natural products. OTC is synthesized by a type II polyketide synthase that generates the poly-beta-ketone backbone through successive decarboxylative condensation of malonyl-CoA extender units, followed by modifications by cyclases, oxygenases, transferases, and additional tailoring enzymes. Genetic and biochemical studies have illuminated most of the steps involved in the biosynthesis of OTC, which is detailed here as a representative case study in type II polyketide biosynthesis.
    MeSH term(s) Anti-Bacterial Agents/biosynthesis ; Anti-Bacterial Agents/chemistry ; Cyclization ; Drug Resistance, Bacterial/genetics ; Macrolides/metabolism ; Oxytetracycline/biosynthesis ; Oxytetracycline/chemistry ; Tetracyclines/metabolism
    Chemical Substances Anti-Bacterial Agents ; Macrolides ; Tetracyclines ; 4-epianhydrotetracycline (680VDL31MX) ; Oxytetracycline (X20I9EN955)
    Language English
    Publishing date 2010-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.R110.130419
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Oxytetracycline Biosynthesis

    Pickens, Lauren B / Tang, Yi

    Journal of biological chemistry. 2010 Sept. 3, v. 285, no. 36

    2010  

    Abstract: Oxytetracycline (OTC) is a broad-spectrum antibiotic that acts by inhibiting protein synthesis in bacteria. It is an important member of the bacterial aromatic polyketide family, which is a structurally diverse class of natural products. OTC is ... ...

    Abstract Oxytetracycline (OTC) is a broad-spectrum antibiotic that acts by inhibiting protein synthesis in bacteria. It is an important member of the bacterial aromatic polyketide family, which is a structurally diverse class of natural products. OTC is synthesized by a type II polyketide synthase that generates the poly-β-ketone backbone through successive decarboxylative condensation of malonyl-CoA extender units, followed by modifications by cyclases, oxygenases, transferases, and additional tailoring enzymes. Genetic and biochemical studies have illuminated most of the steps involved in the biosynthesis of OTC, which is detailed here as a representative case study in type II polyketide biosynthesis.
    Language English
    Dates of publication 2010-0903
    Size p. 27509-27515.
    Publishing place American Society for Biochemistry and Molecular Biology
    Document type Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Decoding and engineering tetracycline biosynthesis.

    Pickens, Lauren B / Tang, Yi

    Metabolic engineering

    2008  Volume 11, Issue 2, Page(s) 69–75

    Abstract: Tetracyclines have been important agents in combating infectious disease since their discovery in the mid-20th century. Following widespread use, tetracycline resistance mechanisms emerged and continue to create a need for new derivatives that are active ...

    Abstract Tetracyclines have been important agents in combating infectious disease since their discovery in the mid-20th century. Following widespread use, tetracycline resistance mechanisms emerged and continue to create a need for new derivatives that are active against resistant bacterial strains. Semisynthesis has led to second and third generation tetracycline derivatives with enhanced antibiotic activity and pharmacological properties. Recent advancement in understanding of the tetracycline biosynthetic pathway may open the door to broaden the range of tetracycline derivatives and afford analogs that are difficult to access by synthetic chemistry.
    MeSH term(s) Models, Biological ; Protein Engineering/methods ; Recombinant Proteins/metabolism ; Signal Transduction/physiology ; Streptomyces/physiology ; Tetracycline/biosynthesis
    Chemical Substances Recombinant Proteins ; Tetracycline (F8VB5M810T)
    Language English
    Publishing date 2008-10-22
    Publishing country Belgium
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1470383-x
    ISSN 1096-7184 ; 1096-7176
    ISSN (online) 1096-7184
    ISSN 1096-7176
    DOI 10.1016/j.ymben.2008.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Metabolic engineering for the production of natural products.

    Pickens, Lauren B / Tang, Yi / Chooi, Yit-Heng

    Annual review of chemical and biomolecular engineering

    2012  Volume 2, Page(s) 211–236

    Abstract: Natural products and their derivatives play an important role in modern healthcare as frontline treatments for many diseases and as inspiration for chemically synthesized therapeutics. With advances in sequencing and recombinant DNA technology, many of ... ...

    Abstract Natural products and their derivatives play an important role in modern healthcare as frontline treatments for many diseases and as inspiration for chemically synthesized therapeutics. With advances in sequencing and recombinant DNA technology, many of the biosynthetic pathways responsible for the production of these chemically complex yet valuable compounds have been elucidated. With an ever-expanding toolkit of biosynthetic components, metabolic engineering is an increasingly powerful method to improve natural product titers and generate novel compounds. Heterologous production platforms have enabled access to pathways from difficult to culture strains, systems biology and metabolic modeling tools have resulted in increasing predictive and analytic capabilities, advances in expression systems and regulation have enabled the fine-tuning of pathways for increased efficiency, and characterization of individual pathway components has facilitated the construction of hybrid pathways for the production of new compounds. These advances in the many aspects of metabolic engineering not only have yielded fascinating scientific discoveries but also make it an increasingly viable approach for the optimization of natural product biosynthesis.
    MeSH term(s) Bacteria/chemistry ; Bacteria/metabolism ; Biological Products/chemical synthesis ; Biological Products/chemistry ; Biological Products/metabolism ; Biological Products/therapeutic use ; Biotechnology/methods ; Fungi/chemistry ; Fungi/metabolism ; Metabolic Engineering/methods ; Molecular Structure ; Plants/chemistry ; Plants/metabolism ; Protein Engineering/methods
    Chemical Substances Biological Products
    Language English
    Publishing date 2012-03-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 2516755-8
    ISSN 1947-5446 ; 1947-5438
    ISSN (online) 1947-5446
    ISSN 1947-5438
    DOI 10.1146/annurev-chembioeng-061010-114209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Heterologous expression and manipulation of three tetracycline biosynthetic pathways.

    Wang, Peng / Kim, Woncheol / Pickens, Lauren B / Gao, Xue / Tang, Yi

    Angewandte Chemie (International ed. in English)

    2012  Volume 51, Issue 44, Page(s) 11136–11140

    Abstract: A very accommodating host: Three tetracycline biosynthetic pathways were overexpressed and manipulated in the heterologous host Streptomyces lividans K4-114. Through the inactivation of various genes and characterization of the resulting biosynthetic ... ...

    Abstract A very accommodating host: Three tetracycline biosynthetic pathways were overexpressed and manipulated in the heterologous host Streptomyces lividans K4-114. Through the inactivation of various genes and characterization of the resulting biosynthetic intermediates, new tetracycline-modifying enzymes were identified (see scheme).
    MeSH term(s) Chlortetracycline/analogs & derivatives ; Chlortetracycline/biosynthesis ; Chlortetracycline/chemistry ; Chlortetracycline/isolation & purification ; Chromatography, High Pressure Liquid ; Molecular Structure ; Oxytetracycline/biosynthesis ; Oxytetracycline/chemistry ; Oxytetracycline/isolation & purification ; Streptomyces/chemistry ; Streptomyces/metabolism ; Tetracyclines/biosynthesis ; Tetracyclines/chemistry ; Tetracyclines/isolation & purification
    Chemical Substances Tetracyclines ; dactylocycline A (125622-12-0) ; SF 2575 (126728-71-0) ; Chlortetracycline (WCK1KIQ23Q) ; Oxytetracycline (X20I9EN955)
    Language English
    Publishing date 2012-09-28
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.201205426
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Structural and biochemical characterization of the salicylyl-acyltranferase SsfX3 from a tetracycline biosynthetic pathway.

    Pickens, Lauren B / Sawaya, Michael R / Rasool, Huma / Pashkov, Inna / Yeates, Todd O / Tang, Yi

    The Journal of biological chemistry

    2011  Volume 286, Issue 48, Page(s) 41539–41551

    Abstract: SsfX3 is a GDSL family acyltransferase that transfers salicylate to the C-4 hydroxyl of a tetracycline intermediate in the penultimate step during biosynthesis of the anticancer natural product SF2575. The C-4 salicylate takes the place of the more ... ...

    Abstract SsfX3 is a GDSL family acyltransferase that transfers salicylate to the C-4 hydroxyl of a tetracycline intermediate in the penultimate step during biosynthesis of the anticancer natural product SF2575. The C-4 salicylate takes the place of the more common C-4 dimethylamine functionality, making SsfX3 the first acyltransferase identified to act on a tetracycline substrate. The crystal structure of SsfX3 was determined at 2.5 Å, revealing two distinct domains as follows: an N-terminal β-sandwich domain that resembles a carbohydrate-binding module, and a C-terminal catalytic domain that contains the atypical α/β-hydrolase fold found in the GDSL hydrolase family of enzymes. The active site lies at one end of a large open binding pocket, which is spatially defined by structural elements from both the N- and C-terminal domains. Mutational analysis in the putative substrate binding pocket identified residues from both domains that are important for binding the acyl donor and acceptor. Furthermore, removal of the N-terminal carbohydrate-binding module-like domain rendered the stand-alone α/β-hydrolase domain inactive. The additional noncatalytic module is therefore proposed to be required to define the binding pocket and provide sufficient interactions with the spatially extended tetracyclic substrate. SsfX3 was also demonstrated to accept a variety of non-native acyl groups. This relaxed substrate specificity toward the acyl donor allowed the chemoenzymatic biosynthesis of C-4-modified analogs of the immediate precursor to the bioactive SF2575; these were used to assay the structure activity relationships at the C-4 position.
    MeSH term(s) Acyltransferases/chemistry ; Acyltransferases/genetics ; Acyltransferases/metabolism ; Amino Acid Substitution ; Binding Sites ; Crystallography, X-Ray ; Mutation, Missense ; Protein Structure, Tertiary ; Streptomyces/enzymology ; Streptomyces/genetics ; Tetracyclines/biosynthesis ; Tetracyclines/chemistry
    Chemical Substances Tetracyclines ; SF 2575 (126728-71-0) ; Acyltransferases (EC 2.3.-)
    Language English
    Publishing date 2011-09-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1074/jbc.M111.299859
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Biochemical analysis of the biosynthetic pathway of an anticancer tetracycline SF2575.

    Pickens, Lauren B / Kim, Woncheol / Wang, Peng / Zhou, Hui / Watanabe, Kenji / Gomi, Shuichi / Tang, Yi

    Journal of the American Chemical Society

    2009  Volume 131, Issue 48, Page(s) 17677–17689

    Abstract: SF2575 1 is a tetracycline polyketide produced by Streptomyces sp. SF2575 and displays exceptionally potent anticancer activity toward a broad range of cancer cell lines. The structure of SF2575 is characterized by a highly substituted tetracycline ... ...

    Abstract SF2575 1 is a tetracycline polyketide produced by Streptomyces sp. SF2575 and displays exceptionally potent anticancer activity toward a broad range of cancer cell lines. The structure of SF2575 is characterized by a highly substituted tetracycline aglycon. The modifications include methylation of the C-6 and C-12a hydroxyl groups, acylation of the 4-(S)-hydroxyl with salicylic acid, C-glycosylation of the C-9 of the D-ring with D-olivose and further acylation of the C4'-hydroxyl of D-olivose with the unusual angelic acid. Understanding the biosynthesis of SF2575 can therefore expand the repertoire of enzymes that can modify tetracyclines, and facilitate engineered biosynthesis of SF2575 analogues. In this study, we identified, sequenced, and functionally analyzed the ssf biosynthetic gene cluster which contains 40 putative open reading frames. Genes encoding enzymes that can assemble the tetracycline aglycon, as well as installing these unique structural features, are found in the gene cluster. Biosynthetic intermediates were isolated from the SF2575 culture extract to suggest the order of pendant-group addition is C-9 glycosylation, C-4 salicylation, and O-4' angelylcylation. Using in vitro assays, two enzymes that are responsible for C-4 acylation of salicylic acid were identified. These enzymes include an ATP-dependent salicylyl-CoA ligase SsfL1 and a putative GDSL family acyltransferase SsfX3, both of which were shown to have relaxed substrate specificity toward substituted benzoic acids. Since the salicylic acid moiety is critically important for the anticancer properties of SF2575, verification of the activities of SsfL1 and SsfX3 sets the stage for biosynthetic modification of the C-4 group toward structure-activity relationship studies of SF2575. Using heterologous biosynthesis in Streptomyces lividans, we also determined that biosynthesis of the SF2575 tetracycline aglycon 8 parallels that of oxytetracycline 4 and diverges after the assembly of 4-keto-anhydrotetracycline 51. The minimal ssf polyketide synthase together with the amidotransferase SsfD produced the amidated decaketide backbone that is required for the formation of 2-naphthacenecarboxamide skeleton. Additional enzymes, such as cyclases C-6 methyltransferase and C-4/C-12a dihydroxylase, were functionally reconstituted.
    MeSH term(s) Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Carboxylic Acids/metabolism ; Cell Line, Tumor ; Complex Mixtures/chemistry ; Computational Biology ; Deoxy Sugars/biosynthesis ; Fermentation ; Humans ; Inhibitory Concentration 50 ; Macrolides/metabolism ; Multigene Family ; Salicylates/metabolism ; Sequence Analysis, DNA ; Streptomyces/enzymology ; Streptomyces/genetics ; Streptomyces/metabolism ; Substrate Specificity ; Tetracyclines/biosynthesis ; Tetracyclines/pharmacology
    Chemical Substances Antineoplastic Agents ; Bacterial Proteins ; Carboxylic Acids ; Complex Mixtures ; Deoxy Sugars ; Macrolides ; Salicylates ; Tetracyclines ; SF 2575 (126728-71-0) ; olivose (6988-55-2)
    Language English
    Publishing date 2009-11-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3155-0
    ISSN 1520-5126 ; 0002-7863
    ISSN (online) 1520-5126
    ISSN 0002-7863
    DOI 10.1021/ja907852c
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Characteristics of a Multistate Outbreak of Lung Injury Associated with E-cigarette Use, or Vaping - United States, 2019.

    Perrine, Cria G / Pickens, Cassandra M / Boehmer, Tegan K / King, Brian A / Jones, Christopher M / DeSisto, Carla L / Duca, Lindsey M / Lekiachvili, Akaki / Kenemer, Brandon / Shamout, Mays / Landen, Michael G / Lynfield, Ruth / Ghinai, Isaac / Heinzerling, Amy / Lewis, Nathaniel / Pray, Ian W / Tanz, Lauren J / Patel, Anita / Briss, Peter A

    MMWR. Morbidity and mortality weekly report

    2019  Volume 68, Issue 39, Page(s) 860–864

    Abstract: Electronic cigarettes (e-cigarettes), also called vapes, e-hookas, vape pens, tank systems, mods, and electronic nicotine delivery systems (ENDS), are electronic devices that produce an aerosol by heating a liquid typically containing nicotine, ... ...

    Abstract Electronic cigarettes (e-cigarettes), also called vapes, e-hookas, vape pens, tank systems, mods, and electronic nicotine delivery systems (ENDS), are electronic devices that produce an aerosol by heating a liquid typically containing nicotine, flavorings, and other additives; users inhale this aerosol into their lungs (1). E-cigarettes also can be used to deliver tetrahydrocannabinol (THC), the principal psychoactive component of cannabis (1). Use of e-cigarettes is commonly called vaping. Lung injury associated with e-cigarette use, or vaping, has recently been reported in most states (2-4). CDC, the Food and Drug Administration (FDA), state and local health departments, and others are investigating this outbreak. This report provides data on patterns of the outbreak and characteristics of patients, including sex, age, and selected substances used in e-cigarette, or vaping, products reported to CDC as part of this ongoing multistate investigation. As of September 24, 2019, 46 state health departments and one territorial health department had reported 805 patients with cases of lung injury associated with use of e-cigarette, or vaping, products to CDC. Sixty-nine percent of patients were males, and the median age was 23 years (range = 13-72 years). To date, 12 deaths have been confirmed in 10 states. Among 514 patients with information on substances used in e-cigarettes, or vaping products, in the 30 days preceding symptom onset, 76.9% reported using THC-containing products, and 56.8% reported using nicotine-containing products; 36.0% reported exclusive use of THC-containing products, and 16.0% reported exclusive use of nicotine-containing products. The specific chemical exposure(s) causing the outbreak is currently unknown. While this investigation is ongoing, CDC recommends that persons consider refraining from using e-cigarette, or vaping, products, particularly those containing THC. CDC will continue to work in collaboration with FDA and state and local partners to investigate cases and advise and alert the public on the investigation as additional information becomes available.
    MeSH term(s) Adolescent ; Adult ; Aged ; Disease Outbreaks ; Dronabinol/adverse effects ; Electronic Nicotine Delivery Systems ; Female ; Humans ; Lung Injury/epidemiology ; Male ; Middle Aged ; United States/epidemiology ; Vaping/adverse effects ; Young Adult
    Chemical Substances Dronabinol (7J8897W37S)
    Language English
    Publishing date 2019-10-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 412775-4
    ISSN 1545-861X ; 0149-2195
    ISSN (online) 1545-861X
    ISSN 0149-2195
    DOI 10.15585/mmwr.mm6839e1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation

    Malta, Tathiane M. / Sokolov, Artëm / Gentles, Andrew J. / Burzykowski, Tomasz / Poisson, Laila / Weinstein, John N. / Kaminska, B. / Huelsken, Joerg / Omberg, Larsson / Gevaert, Olivier / Colaprico, Antonio / Czerwińska, Patrycja / Mazurek, Sylwia / Mishra, Lopa / Heyn, Holger / Krasnitz, Alex / Godwin, Andrew K. / Lazar, Alexander / Stuart, Joshua M. /
    Hoadley, Katherine A. / Laird, Peter W. / Noushmehr, Houtan / Wiznerowicz, Maciej / Caesar-Johnson, Samantha J. / Demchok, John A. / Felau, Ina / Kasapi, Melpomeni / Ferguson, Martin L. / Hutter, Carolyn M. / Sofia, Heidi J. / Tarnuzzer, Roy / Wang, Zhining / Yang, Liming / Zenklusen, Jean C. / Zhang, Jiashan (Julia) / Chudamani, Sudha / Liu, Jia / Lolla, Laxmi / Naresh, Rashi / Pihl, Todd / Sun, Qiang / Wan, Yunhu / Wu, Ye / Cho, Juok / DeFreitas, Timothy / Frazer, Scott / Gehlenborg, Nils / Getz, Gad / Heiman, David I. / Kim, Jaegil / Lawrence, Michael S. / Lin, Pei / Meier, Samuel A. / Noble, Michael S. / Saksena, Gordon / Voet, Doug / Zhang, Hailei / Bernard, Brady / Chambwe, Nyasha / Dhankani, Varsha / Knijnenburg, Theo / Kramer, Roger / Leinonen, Kalle / Liu, Yuexin / Miller, Michael / Reynolds, Sheila / Shmulevich, Ilya / Thorsson, Vesteinn / Zhang, Wei / Akbani, Rehan / Broom, Bradley M. / Hegde, Apurva M. / Ju, Zhenlin / Kanchi, Rupa S. / Korkut, Anil / Li, Jun / Liang, Han / Ling, Shiyun / Liu, Wenbin / Lu, Yiling / Mills, Gordon B. / Ng, Kwok-Shing / Rao, Arvind / Ryan, Michael / Wang, Jing / Zhang, Jiexin / Abeshouse, Adam / Armenia, Joshua / Chakravarty, Debyani / Chatila, Walid K. / de Bruijn, Ino / Gao, Jianjiong / Gross, Benjamin E. / Heins, Zachary J. / Kundra, Ritika / La, Konnor / Ladanyi, Marc / Luna, Augustin / Nissan, Moriah G. / Ochoa, Angelica / Phillips, Sarah M. / Reznik, Ed / Sanchez-Vega, Francisco / Sander, Chris / Schultz, Nikolaus / Sheridan, Robert / Sumer, S. Onur / Sun, Yichao / Taylor, Barry S. / Wang, Jioajiao / Zhang, Hongxin / Anur, Pavana / Peto, Myron / Spellman, Paul / Benz, Christopher / Wong, Christopher K. / Yau, Christina / Hayes, D. Neil / Parker, Joel S. / Wilkerson, Matthew D. / Ally, Adrian / Balasundaram, Miruna / Bowlby, Reanne / Brooks, Denise / Carlsen, Rebecca / Chuah, Eric / Dhalla, Noreen / Holt, Robert / Jones, Steven J.M. / Kasaian, Katayoon / Lee, Darlene / Ma, Yussanne / Marra, Marco A. / Mayo, Michael / Moore, Richard A. / Mungall, Andrew J. / Mungall, Karen / Robertson, A. Gordon / Sadeghi, Sara / Schein, Jacqueline E. / Sipahimalani, Payal / Tam, Angela / Thiessen, Nina / Tse, Kane / Wong, Tina / Berger, Ashton C. / Beroukhim, Rameen / Cherniack, Andrew D. / Cibulskis, Carrie / Gabriel, Stacey B. / Gao, Galen F. / Ha, Gavin / Meyerson, Matthew / Schumacher, Steven E. / Shih, Juliann / Kucherlapati, Melanie H. / Kucherlapati, Raju S. / Baylin, Stephen / Cope, Leslie / Danilova, Ludmila / Bootwalla, Moiz S. / Lai, Phillip H. / Maglinte, Dennis T. / Van Den Berg, David J. / Weisenberger, Daniel J. / Auman, J. Todd / Balu, Saianand / Bodenheimer, Thomas / Fan, Cheng / Hoyle, Alan P. / Jefferys, Stuart R. / Jones, Corbin D. / Meng, Shaowu / Mieczkowski, Piotr A. / Mose, Lisle E. / Perou, Amy H. / Perou, Charles M. / Roach, Jeffrey / Shi, Yan / Simons, Janae V. / Skelly, Tara / Soloway, Matthew G. / Tan, Donghui / Veluvolu, Umadevi / Fan, Huihui / Hinoue, Toshinori / Shen, Hui / Zhou, Wanding / Bellair, Michelle / Chang, Kyle / Covington, Kyle / Creighton, Chad J. / Dinh, Huyen / Doddapaneni, HarshaVardhan / Donehower, Lawrence A. / Drummond, Jennifer / Gibbs, Richard / Glenn, Robert / Hale, Walker / Han, Yi / Hu, Jianhong / Korchina, Viktoriya / Lee, Sandra / Lewis, Lora / Li, Wei / Liu, Xiuping / Morgan, Margaret / Morton, Donna / Muzny, Donna / Santibanez, Jireh / Sheth, Margi / Shinbrot, Eve / Wang, Linghua / Wang, Min / Wheeler, David A. / Xi, Liu / Zhao, Fengmei / Hess, Julian / Appelbaum, Elizabeth L. / Bailey, Matthew / Cordes, Matthew G. / Ding, Li / Fronick, Catrina C. / Fulton, Lucinda A. / Fulton, Robert S. / Kandoth, Cyriac / Mardis, Elaine R. / McLellan, Michael D. / Miller, Christopher A. / Schmidt, Heather K. / Wilson, Richard K. / Crain, Daniel / Curley, Erin / Gardner, Johanna / Lau, Kevin / Mallery, David / Morris, Scott / Paulauskis, Joseph / Penny, Robert / Shelton, Candace / Shelton, Troy / Sherman, Mark / Thompson, Eric / Yena, Peggy / Bowen, Jay / Gastier-Foster, Julie M. / Gerken, Mark / Leraas, Kristen M. / Lichtenberg, Tara M. / Ramirez, Nilsa C. / Wise, Lisa / Zmuda, Erik / Corcoran, Niall / Costello, Tony / Hovens, Christopher / Carvalho, Andre L. / de Carvalho, Ana C. / Fregnani, José H. / Filho, Adhemar Longatto / Reis, Rui M. / Scapulatempo-Neto, Cristovam / Silveira, Henrique C.S. / Vidal, Daniel O. / Burnette, Andrew / Eschbacher, Jennifer / Hermes, Beth / Noss, Ardene / Singh, Rosy / Anderson, Matthew L. / Castro, Patricia D. / Ittmann, Michael / Huntsman, David / Kohl, Bernard / Lệ Xuân / Thorp, Richard / Andry, Chris / Duffy, Elizabeth R. / Lyadov, Vladimir / Paklina, Oxana / Setdikova, Galiya / Shabunin, Alexey / Tavobilov, Mikhail / McPherson, Christopher / Warnick, Ronald / Berkowitz, Ross / Cramer, Daniel / Feltmate, Colleen / Horowitz, Neil / Kibel, Adam / Muto, Michael / Raut, Chandrajit P. / Malykh, Andrei / Barnholtz-Sloan, Jill S. / Barrett, Wendi / Devine, Karen / Fulop, Jordonna / Ostrom, Quinn T. / Shimmel, Kristen / Wolinsky, Yingli / Sloan, Andrew E. / De Rose, Agostino / Giuliante, Felice / Goodman, Marc / Karlan, Beth Y. / Hagedorn, C. H. / Eckman, John / Harr, Jodi / Myers, Jerome / Tucker, Kelinda / Zach, Leigh Anne / Deyarmin, Brenda / Hu, Hai / Kvecher, Leonid / Larson, Caroline / Mural, Richard J. / Somiari, Stella / Vicha, Ales / Zelinka, Tomas / Bennett, Joseph / Iacocca, Mary / Rabeno, Brenda / Swanson, Patricia / Latour, Mathieu / Lacombe, Louis / Têtu, Bernard / Bergeron, Alain / McGraw, Mary / Staugaitis, Susan M. / Chabot, John / Hibshoosh, Hanina / Sepulveda, Antonia / Su, Tao / Wang, Timothy / Potapova, Olga / Voronina, Olga / Desjardins, Laurence / Mariani, Odette / Roman-Roman, Sergio / Sastre, Xavier / Stern, Marc-Henri / Cheng, Feixiong / Signoretti, Sabina / Berchuck, Andrew / Bigner, Darell / Lipp, Eric / Marks, Jeffrey / McCall, Shannon / McLendon, Roger / Secord, Angeles / Sharp, Alexis / Behera, Madhusmita / Brat, Daniel J. / Chen, Amy / Delman, Keith / Force, Seth / Khuri, Fadlo / Magliocca, Kelly / Maithel, Shishir / Olson, Jeffrey J. / Owonikoko, Taofeek / Pickens, Alan / Ramalingam, Suresh / Shin, Dong M. / Sica, Gabriel / Van Meir, Erwin G. / Zhang, Hongzheng / Eijckenboom, Wil / Gillis, Ad / Korpershoek, Esther / Looijenga, Leendert / Oosterhuis, Wolter / Stoop, Hans / van Kessel, Kim E. / Zwarthoff, Ellen C. / Calatozzolo, Chiara / Cuppini, Lucia / Cuzzubbo, Stefania / DiMeco, Francesco / Finocchiaro, Gaetano / Mattei, Luca / Perin, Alessandro / Pollo, Bianca / Chen, Chu / Houck, John / Lohavanichbutr, Pawadee / Hartmann, Arndt / Stoehr, Christine / Stoehr, Robert / Taubert, Helge / Wach, Sven / Wullich, Bernd / Kycler, Witold / Murawa, Dawid / Chung, Ki / Edenfield, W. Jeffrey / Martin, Julie / Baudin, Eric / Bubley, Glenn / Bueno, Raphael / De Rienzo, Assunta / Richards, William G. / Kalkanis, Steven / Mikkelsen, Tom / Scarpace, Lisa / Girard, Nicolas / Aymerich, Marta / Campo, Elias / Giné, Eva / Guillermo, Armando López / Van Bang, Nguyen / Hanh, Phan Thi / Phu, Bui Duc / Tang, Yufang / Colman, Howard / Evason, Kimberley / Dottino, Peter R. / Martignetti, John A. / Gabra, Hani / Juhl, Hartmut / Akeredolu, Teniola / Stepa, Serghei / Hoon, Dave / Ahn, Keunsoo / Kang, Koo Jeong / Beuschlein, Felix / Breggia, Anne / Birrer, Michael / Bell, Debra / Borad, Mitesh / Bryce, Alan H. / Castle, Erik / Chandan, Vishal / Cheville, John / Copland, John A. / Farnell, Michael / Flotte, Thomas / Giama, Nasra / Ho, Thai / Kendrick, Michael / Kocher, Jean-Pierre / Kopp, Karla / Moser, Catherine / Nagorney, David / O’Brien, Daniel / O’Neill, Brian Patrick / Patel, Tushar / Petersen, Gloria / Que, Florencia / Rivera, Michael / Roberts, Lewis / Smallridge, Robert / Smyrk, Thomas / Stanton, Melissa / Thompson, R. Houston / Torbenson, Michael / Yang, Ju Dong / Zhang, Lizhi / Brimo, Fadi / Ajani, Jaffer A. / Gonzalez, Ana Maria Angulo / Behrens, Carmen / Bondaruk, Jolanta / Broaddus, Russell / Czerniak, Bogdan / Esmaeli, Bita / Fujimoto, Junya / Gershenwald, Jeffrey / Guo, Charles / Logothetis, Christopher / Meric-Bernstam, Funda / Moran, Cesar / Ramondetta, Lois / Rice, David / Sood, Anil / Tamboli, Pheroze / Thompson, Timothy / Troncoso, Patricia / Tsao, Anne / Wistuba, Ignacio / Carter, Candace / Haydu, Lauren / Hersey, Peter / Jakrot, Valerie / Kakavand, Hojabr / Kefford, Richard / Lee, Kenneth / Long, Georgina / Mann, Graham / Quinn, Michael / Saw, Robyn / Scolyer, Richard / Shannon, Kerwin / Spillane, Andrew / Stretch, Jonathan / Synott, Maria / Thompson, John / Wilmott, James / Al-Ahmadie, Hikmat / Chan, Timothy A. / Ghossein, Ronald / Gopalan, Anuradha / Levine, Douglas A. / Reuter, Victor / Singer, Samuel / Singh, Bhuvanesh / Tien, Nguyen Viet / Broudy, Thomas / Mirsaidi, Cyrus / Nair, Praveen / Drwiega, Paul / Miller, Judy / Smith, Jennifer / Zaren, Howard / Park, Joong-Won / Hung, Nguyen Phi / Kebebew, Electron / Linehan, Marston / Metwalli, Adam R. / Pacak, Karel / Pinto, Peter A. / Schiffman, Mark / Schmidt, Laura S. / Vocke, Cathy D. / Wentzensen, Nicolas / Worrell, Robert / Yang, Hannah / Moncrieff, Marc / Goparaju, Chandra / Melamed, Jonathan / Pass, Harvey / Botnariuc, Natalia / Caraman, Irina / Cernat, Mircea / Chemencedji, Inga / Clipca, Adrian / Doruc, Serghei / Gorincioi, Ghenadie / Mura, Sergiu / Pirtac, Maria / Stancul, Irina / Tcaciuc, Diana / Albert, Monique / Alexopoulou, Iakovina / Arnaout, Angel / Bartlett, John / Engel, Jay / Gilbert, Sebastien / Parfitt, Jeremy / Sekhon, Harman / Thomas, George / Rassl, Doris M. / Rintoul, Robert C. / Bifulco, Carlo / Tamakawa, Raina / Urba, Walter / Hayward, Nicholas / Timmers, Henri / Antenucci, Anna / Facciolo, Francesco / Grazi, Gianluca / Marino, Mirella / Merola, Roberta / de Krijger, Ronald / Gimenez-Roqueplo, Anne-Paule / Piché, Alain / Chevalier, Simone / McKercher, Ginette / Birsoy, Kivanc / Barnett, Gene / Brewer, Cathy / Farver, Carol / Naska, Theresa / Pennell, Nathan A. / Raymond, Daniel / Schilero, Cathy / Smolenski, Kathy / Williams, F. / Morrison, Carl / Borgia, Jeffrey A. / Liptay, Michael J. / Pool, Mark / Seder, Christopher W. / Junker, Kerstin / Dinkin, Mikhail / Manikhas, George / Alvaro, Domenico / Bragazzi, Maria Consiglia / Cardinale, Vincenzo / Carpino, Guido / Gaudio, Eugenio / Chesla, David / Cottingham, Sandra / Dubina, Michael / Moiseenko, Fedor / Dhanasekaran, Renumathy / Becker, Karl Friedrich / Janssen, Klaus-Peter / Slotta-Huspenina, Julia / Abdel-Rahman, Mohamed H. / Aziz, Dina / Bell, Sue / Cebulla, Colleen M. / Davis, Amy / Duell, Rebecca / Elder, J. Bradley / Hilty, Joe / Kumar, Bahavna / Lang, James / Lehman, Norman L. / Mandt, Randy / Nguyen, Phuong / Pilarski, Robert / Rai, Karan / Schoenfield, Lynn / Senecal, Kelly / Wakely, Paul / Hansen, Paul / Lechan, Ronald / Powers, James / Tischler, Arthur / Grizzle, William E. / Sexton, Katherine C. / Kastl, Alison / Henderson, Joel / Porten, Sima / Waldmann, Jens / Fassnacht, Martin / Asa, Sylvia L. / Schadendorf, Dirk / Couce, Marta / Graefen, Markus / Huland, Hartwig / Sauter, Guido / Schlomm, Thorsten / Simon, Ronald / Tennstedt, Pierre / Olabode, Oluwole / Nelson, Mark / Bathe, Oliver / Carroll, Peter R. / Chan, June M. / Disaia, Philip / Glenn, Pat / Kelley, Robin K. / Landen, Charles N. / Phillips, Joanna / Prados, Michael / Simko, Jeffry / Smith-McCune, Karen / VandenBerg, Scott / Roggin, Kevin / Fehrenbach, Ashley / Kendler, Ady / Sifri, Suzanne / Steele, Ruth / Jimeno, Antonio / Carey, Francis / Forgie, Ian / Mannelli, Massimo / Carney, Michael / Hernandez, Brenda / Campos, Benito / Herold-Mende, Christel / Jungk, Christin / Unterberg, A. / Deimling, Andreas von / Bossler, Aaron / Galbraith, Joseph / Jacobus, Laura / Knudson, Michael / Knutson, Tina / Ma, Deqin / Milhem, Mohammed / Sigmund, Rita / Madan, Rashna / Rosenthal, Howard G. / Adebamowo, Clement / Adebamowo, Sally N. / Boussioutas, Alex / Beer, David / Giordano, Thomas / Mes-Masson, Anne-Marie / Saad, Fred / Bocklage, Therese / Landrum, Lisa / Mannel, Robert / Moore, Kathleen / Moxley, Katherine / Postier, Russel / Walker, Joan / Zuna, Rosemary / Feldman, Michael / Valdivieso, Federico / Dhir, Rajiv / Luketich, James / Pinero, Edna M. Mora / Quintero-Aguilo, Mario / Carlotti, Carlos Gilberto / Santos, José Sebastião dos / Kemp, Rafael / Sankarankuty, Ajith / Tirapelli, Daniela / Catto, James / Agnew, Kathy / Swisher, Elizabeth / Creaney, Jenette / Robinson, Bruce / Shelley, Carl Simon / Godwin, Eryn M. / Kendall, Sara / Shipman, Cassaundra / Bradford, Carol / Carey, Thomas / Haddad, Andrea / Moyer, Jeffey / Peterson, Lisa / Prince, Mark / Rozek, Laura / Wolf, Gregory / Bowman, Rayleen / Fong, Kwun M. / Yang, Ian / Korst, Robert / Rathmell, W. Kimryn / Fantacone-Campbell, J. Leigh / Hooke, Jeffrey A. / Kovatich, Albert J. / Shriver, Craig D. / DiPersio, John / Drake, Bettina / Govindan, Ramaswamy / Heath, Sharon / Ley, Timothy / Van Tine, Brian / Westervelt, Peter / Rubin, Mark A. / Lee, Jung Il / Aredes, Natália D. / Mariamidze, Armaz

    Cell. 2018 Apr. 05, v. 173, no. 2 p.338-354.e15

    2018  

    Abstract: Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative ... ...

    Institution The Cancer Genome Atlas Research Network
    Abstract Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.[Display omitted]
    Keywords algorithms ; artificial intelligence ; epigenetics ; metastasis ; neoplasm progression ; neoplasms ; phenotype ; progeny ; regression analysis ; transcriptomics ; The Cancer Genome Atlas ; stemness ; cancer stem cells ; genomic ; epigenomic ; machine learning ; pan-cancer ; dedifferentiation
    Language English
    Dates of publication 2018-0405
    Size p. 338-354.e15.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note NAL-AP-2-clean ; Resource is Open Access
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.03.034
    Database NAL-Catalogue (AGRICOLA)

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  10. Article ; Online: Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer

    Hoadley, Katherine A. / Yau, Christina / Hinoue, Toshinori / Wolf, Denise M. / Lazar, Alexander / Drill, Esther / Shen, Ronglai / Taylor, Alison M. / Cherniack, Andrew D. / Thorsson, Vésteinn / Akbani, Rehan / Bowlby, Reanne / Wong, Christopher K. / Wiznerowicz, Maciej / Sanchez-Vega, Francisco / Robertson, A. Gordon / Schneider, Barbara G. / Lawrence, Michael S. / Noushmehr, Houtan /
    Malta, Tathiane M. / Stuart, Joshua M. / Benz, Christopher C. / Laird, Peter W. / Caesar-Johnson, Samantha J. / Demchok, John A. / Felau, Ina / Kasapi, Melpomeni / Ferguson, Martin L. / Hutter, Carolyn M. / Sofia, Heidi J. / Tarnuzzer, Roy / Wang, Zhining / Yang, Liming / Zenklusen, Jean C. / Zhang, Jiashan (Julia) / Chudamani, Sudha / Liu, Jia / Lolla, Laxmi / Naresh, Rashi / Pihl, Todd / Sun, Qiang / Wan, Yunhu / Wu, Ye / Cho, Juok / DeFreitas, Timothy / Frazer, Scott / Gehlenborg, Nils / Getz, Gad / Heiman, David I. / Kim, Jaegil / Lin, Pei / Meier, Samuel A. / Noble, Michael S. / Saksena, Gordon / Voet, Doug / Zhang, Hailei / Bernard, Brady / Chambwe, Nyasha / Dhankani, Varsha / Knijnenburg, Theo / Kramer, Roger / Leinonen, Kalle / Liu, Yuexin / Miller, Michael / Reynolds, Sheila / Shmulevich, Ilya / Thorsson, Vesteinn / Zhang, Wei / Broom, Bradley M. / Hegde, Apurva M. / Ju, Zhenlin / Kanchi, Rupa S. / Korkut, Anil / Li, Jun / Liang, Han / Ling, Shiyun / Liu, Wenbin / Lu, Yiling / Mills, Gordon B. / Ng, Kwok-Shing / Rao, Arvind / Ryan, Michael / Wang, Jing / Weinstein, John N. / Zhang, Jiexin / Abeshouse, Adam / Armenia, Joshua / Chakravarty, Debyani / Chatila, Walid K. / de Bruijn, Ino / Gao, Jianjiong / Gross, Benjamin E. / Heins, Zachary J. / Kundra, Ritika / La, Konnor / Ladanyi, Marc / Luna, Augustin / Nissan, Moriah G. / Ochoa, Angelica / Phillips, Sarah M. / Reznik, Ed / Sander, Chris / Schultz, Nikolaus / Sheridan, Robert / Sumer, S. Onur / Sun, Yichao / Taylor, Barry S. / Wang, Jioajiao / Zhang, Hongxin / Anur, Pavana / Peto, Myron / Spellman, Paul / Benz, Christopher / Hayes, D. Neil / Parker, Joel S. / Wilkerson, Matthew D. / Ally, Adrian / Balasundaram, Miruna / Brooks, Denise / Carlsen, Rebecca / Chuah, Eric / Dhalla, Noreen / Holt, Robert / Jones, Steven J.M. / Kasaian, Katayoon / Lee, Darlene / Ma, Yussanne / Marra, Marco A. / Mayo, Michael / Moore, Richard A. / Mungall, Andrew J. / Mungall, Karen / Sadeghi, Sara / Schein, Jacqueline E. / Sipahimalani, Payal / Tam, Angela / Thiessen, Nina / Tse, Kane / Wong, Tina / Berger, Ashton C. / Beroukhim, Rameen / Cibulskis, Carrie / Gabriel, Stacey B. / Gao, Galen F. / Ha, Gavin / Meyerson, Matthew / Schumacher, Steven E. / Shih, Juliann / Kucherlapati, Melanie H. / Kucherlapati, Raju S. / Baylin, Stephen / Cope, Leslie / Danilova, Ludmila / Bootwalla, Moiz S. / Lai, Phillip H. / Maglinte, Dennis T. / Van Den Berg, David J. / Weisenberger, Daniel J. / Auman, J. Todd / Balu, Saianand / Bodenheimer, Thomas / Fan, Cheng / Hoyle, Alan P. / Jefferys, Stuart R. / Jones, Corbin D. / Meng, Shaowu / Mieczkowski, Piotr A. / Mose, Lisle E. / Perou, Amy H. / Perou, Charles M. / Roach, Jeffrey / Shi, Yan / Simons, Janae V. / Skelly, Tara / Soloway, Matthew G. / Tan, Donghui / Veluvolu, Umadevi / Fan, Huihui / Shen, Hui / Zhou, Wanding / Bellair, Michelle / Chang, Kyle / Covington, Kyle / Creighton, Chad J. / Dinh, Huyen / Doddapaneni, HarshaVardhan / Donehower, Lawrence A. / Drummond, Jennifer / Gibbs, Richard / Glenn, Robert / Hale, Walker / Han, Yi / Hu, Jianhong / Korchina, Viktoriya / Lee, Sandra / Lewis, Lora / Li, Wei / Liu, Xiuping / Morgan, Margaret / Morton, Donna / Muzny, Donna / Santibanez, Jireh / Sheth, Margi / Shinbrot, Eve / Wang, Linghua / Wang, Min / Wheeler, David A. / Xi, Liu / Zhao, Fengmei / Hess, Julian / Appelbaum, Elizabeth L. / Bailey, Matthew / Cordes, Matthew G. / Ding, Li / Fronick, Catrina C. / Fulton, Lucinda A. / Fulton, Robert S. / Kandoth, Cyriac / Mardis, Elaine R. / McLellan, Michael D. / Miller, Christopher A. / Schmidt, Heather K. / Wilson, Richard K. / Crain, Daniel / Curley, Erin / Gardner, Johanna / Lau, Kevin / Mallery, David / Morris, Scott / Paulauskis, Joseph / Penny, Robert / Shelton, Candace / Shelton, Troy / Sherman, Mark / Thompson, Eric / Yena, Peggy / Bowen, Jay / Gastier-Foster, Julie M. / Gerken, Mark / Leraas, Kristen M. / Lichtenberg, Tara M. / Ramirez, Nilsa C. / Wise, Lisa / Zmuda, Erik / Corcoran, Niall / Costello, Tony / Hovens, Christopher / Carvalho, Andre L. / de Carvalho, Ana C. / Fregnani, José H. / Filho, Adhemar Longatto / Reis, Rui M. / Scapulatempo-Neto, Cristovam / Silveira, Henrique C.S. / Vidal, Daniel O. / Burnette, Andrew / Eschbacher, Jennifer / Hermes, Beth / Noss, Ardene / Singh, Rosy / Anderson, Matthew L. / Castro, Patricia D. / Ittmann, Michael / Huntsman, David / Kohl, Bernard / Lệ Xuân / Thorp, Richard / Andry, Chris / Duffy, Elizabeth R. / Lyadov, Vladimir / Paklina, Oxana / Setdikova, Galiya / Shabunin, Alexey / Tavobilov, Mikhail / McPherson, Christopher / Warnick, Ronald / Berkowitz, Ross / Cramer, Daniel / Feltmate, Colleen / Horowitz, Neil / Kibel, Adam / Muto, Michael / Raut, Chandrajit P. / Malykh, Andrei / Barnholtz-Sloan, Jill S. / Barrett, Wendi / Devine, Karen / Fulop, Jordonna / Ostrom, Quinn T. / Shimmel, Kristen / Wolinsky, Yingli / Sloan, Andrew E. / De Rose, Agostino / Giuliante, Felice / Goodman, Marc / Karlan, Beth Y. / Hagedorn, C. H. / Eckman, John / Harr, Jodi / Myers, Jerome / Tucker, Kelinda / Zach, Leigh Anne / Deyarmin, Brenda / Hu, Hai / Kvecher, Leonid / Larson, Caroline / Mural, Richard J. / Somiari, Stella / Vicha, Ales / Zelinka, Tomas / Bennett, Joseph / Iacocca, Mary / Rabeno, Brenda / Swanson, Patricia / Latour, Mathieu / Lacombe, Louis / Têtu, Bernard / Bergeron, Alain / McGraw, Mary / Staugaitis, Susan M. / Chabot, John / Hibshoosh, Hanina / Sepulveda, Antonia / Su, Tao / Wang, Timothy / Potapova, Olga / Voronina, Olga / Desjardins, Laurence / Mariani, Odette / Roman-Roman, Sergio / Sastre, Xavier / Stern, Marc-Henri / Cheng, Feixiong / Signoretti, Sabina / Berchuck, Andrew / Bigner, Darell / Lipp, Eric / Marks, Jeffrey / McCall, Shannon / McLendon, Roger / Secord, Angeles / Sharp, Alexis / Behera, Madhusmita / Brat, Daniel J. / Chen, Amy / Delman, Keith / Force, Seth / Khuri, Fadlo / Magliocca, Kelly / Maithel, Shishir / Olson, Jeffrey J. / Owonikoko, Taofeek / Pickens, Alan / Ramalingam, Suresh / Shin, Dong M. / Sica, Gabriel / Van Meir, Erwin G. / Zhang, Hongzheng / Eijckenboom, Wil / Gillis, Ad / Korpershoek, Esther / Looijenga, Leendert / Oosterhuis, Wolter / Stoop, Hans / van Kessel, Kim E. / Zwarthoff, Ellen C. / Calatozzolo, Chiara / Cuppini, Lucia / Cuzzubbo, Stefania / DiMeco, Francesco / Finocchiaro, Gaetano / Mattei, Luca / Perin, Alessandro / Pollo, Bianca / Chen, Chu / Houck, John / Lohavanichbutr, Pawadee / Hartmann, Arndt / Stoehr, Christine / Stoehr, Robert / Taubert, Helge / Wach, Sven / Wullich, Bernd / Kycler, Witold / Murawa, Dawid / Chung, Ki / Edenfield, W. Jeffrey / Martin, Julie / Baudin, Eric / Bubley, Glenn / Bueno, Raphael / De Rienzo, Assunta / Richards, William G. / Kalkanis, Steven / Mikkelsen, Tom / Scarpace, Lisa / Girard, Nicolas / Aymerich, Marta / Campo, Elias / Giné, Eva / Guillermo, Armando López / Van Bang, Nguyen / Hanh, Phan Thi / Phu, Bui Duc / Tang, Yufang / Colman, Howard / Evason, Kimberley / Dottino, Peter R. / Martignetti, John A. / Gabra, Hani / Juhl, Hartmut / Akeredolu, Teniola / Stepa, Serghei / Hoon, Dave / Ahn, Keunsoo / Kang, Koo Jeong / Beuschlein, Felix / Breggia, Anne / Birrer, Michael / Bell, Debra / Borad, Mitesh / Bryce, Alan H. / Castle, Erik / Chandan, Vishal / Cheville, John / Copland, John A. / Farnell, Michael / Flotte, Thomas / Giama, Nasra / Ho, Thai / Kendrick, Michael / Kocher, Jean-Pierre / Kopp, Karla / Moser, Catherine / Nagorney, David / O’Brien, Daniel / O’Neill, Brian Patrick / Patel, Tushar / Petersen, Gloria / Que, Florencia / Rivera, Michael / Roberts, Lewis / Smallridge, Robert / Smyrk, Thomas / Stanton, Melissa / Thompson, R. Houston / Torbenson, Michael / Yang, Ju Dong / Zhang, Lizhi / Brimo, Fadi / Ajani, Jaffer A. / Gonzalez, Ana Maria Angulo / Behrens, Carmen / Bondaruk, olanta / Broaddus, Russell / Czerniak, Bogdan / Esmaeli, Bita / Fujimoto, Junya / Gershenwald, Jeffrey / Guo, Charles / Logothetis, Christopher / Meric-Bernstam, Funda / Moran, Cesar / Ramondetta, Lois / Rice, David / Sood, Anil / Tamboli, Pheroze / Thompson, Timothy / Troncoso, Patricia / Tsao, Anne / Wistuba, Ignacio / Carter, Candace / Haydu, Lauren / Hersey, Peter / Jakrot, Valerie / Kakavand, Hojabr / Kefford, Richard / Lee, Kenneth / Long, Georgina / Mann, Graham / Quinn, Michael / Saw, Robyn / Scolyer, Richard / Shannon, Kerwin / Spillane, Andrew / Stretch, Jonathan / Synott, Maria / Thompson, John / Wilmott, James / Al-Ahmadie, Hikmat / Chan, Timothy A. / Ghossein, Ronald / Gopalan, Anuradha / Levine, Douglas A. / Reuter, Victor / Singer, Samuel / Singh, Bhuvanesh / Tien, Nguyen Viet / Broudy, Thomas / Mirsaidi, Cyrus / Nair, Praveen / Drwiega, Paul / Miller, Judy / Smith, Jennifer / Zaren, Howard / Park, Joong-Won / Hung, Nguyen Phi / Kebebew, Electron / Linehan, Marston / Metwalli, Adam R. / Pacak, Karel / Pinto, Peter A. / Schiffman, Mark / Schmidt, Laura S. / Vocke, Cathy D. / Wentzensen, Nicolas / Worrell, Robert / Yang, Hannah / Moncrieff, Marc / Goparaju, Chandra / Melamed, Jonathan / Pass, Harvey / Botnariuc, Natalia / Caraman, Irina / Cernat, Mircea / Chemencedji, Inga / Clipca, Adrian / Doruc, Serghei / Gorincioi, Ghenadie / Mura, Sergiu / Pirtac, Maria / Stancul, Irina / Tcaciuc, Diana / Albert, Monique / Alexopoulou, Iakovina / Arnaout, Angel / Bartlett, John / Engel, Jay / Gilbert, Sebastien / Parfitt, Jeremy / Sekhon, Harman / Thomas, George / Rassl, Doris M. / Rintoul, Robert C. / Bifulco, Carlo / Tamakawa, Raina / Urba, Walter / Hayward, Nicholas / Timmers, Henri / Antenucci, Anna / Facciolo, Francesco / Grazi, Gianluca / Marino, Mirella / Merola, Roberta / de Krijger, Ronald / Gimenez-Roqueplo, Anne-Paule / Piché, Alain / Chevalier, Simone / McKercher, Ginette / Birsoy, Kivanc / Barnett, Gene / Brewer, Cathy / Farver, Carol / Naska, Theresa / Pennell, Nathan A. / Raymond, Daniel / Schilero, Cathy / Smolenski, Kathy / Williams, F. / Morrison, Carl / Borgia, Jeffrey A. / Liptay, Michael J. / Pool, Mark / Seder, Christopher W. / Junker, Kerstin / Omberg, Larsson / Dinkin, Mikhail / Manikhas, George / Alvaro, Domenico / Bragazzi, Maria Consiglia / Cardinale, Vincenzo / Carpino, Guido / Gaudio, Eugenio / Chesla, David / Cottingham, Sandra / Dubina, Michael / Moiseenko, Fedor / Dhanasekaran, Renumathy / Becker, Karl Friedrich / Janssen, Klaus-Peter / Slotta-Huspenina, Julia / Abdel-Rahman, Mohamed H. / Aziz, Dina / Bell, Sue / Cebulla, Colleen M. / Davis, Amy / Duell, Rebecca / Elder, J. 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    Elsevier Inc. Cell. 2018 Apr. 05, v. 173, no. 2 p.291-304.e6

    2018  

    Abstract: We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on ... ...

    Institution The Cancer Genome Atlas Network
    Abstract We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA hypermethylation, mRNA, and miRNA expression levels and reverse-phase protein arrays, of which all, except for aneuploidy, revealed clustering primarily organized by histology, tissue type, or anatomic origin. The influence of cell type was evident in DNA-methylation-based clustering, even after excluding sites with known preexisting tissue-type-specific methylation. Integrative clustering further emphasized the dominant role of cell-of-origin patterns. Molecular similarities among histologically or anatomically related cancer types provide a basis for focused pan-cancer analyses, such as pan-gastrointestinal, pan-gynecological, pan-kidney, and pan-squamous cancers, and those related by stemness features, which in turn may inform strategies for future therapeutic development.
    Keywords DNA hypermethylation ; aneuploidy ; genome ; histology ; microRNA ; therapeutics ; cancer ; TCGA ; transcriptome ; proteome ; methylome ; subtypes ; tissues ; organs ; cell-of-origin
    Language English
    Dates of publication 2018-0405
    Size p. 291-304.e6.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    Note NAL-AP-2-clean ; Resource is Open Access
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2018.03.022
    Database NAL-Catalogue (AGRICOLA)

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