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Book ; Online: A Practical Guide to Teaching Mathematics in the Secondary School

Lee, Clare / Johnston-Wilder, Sue / Ward-Penny, Robert

(Routledge Teaching Guides)

2012

Abstract: A Practical Guide to Teaching Mathematics in the Secondary School offers straightforward advice, inspiration and support for mathematics teachers whether in training or newly qualified. Based on the best research and practice available, it offers a wide ... ...

Series title	Routledge Teaching Guides
Abstract	A Practical Guide to Teaching Mathematics in the Secondary School offers straightforward advice, inspiration and support for mathematics teachers whether in training or newly qualified. Based on the best research and practice available, it offers a wide range of tried and tested approaches that succeed in secondary classrooms. Each chapter contains a wealth of tasks and ideas that allow teachers to reflect on the approaches and make plans for using them in their own classrooms, and offers ideas for lesson plans, learning activities and suggested further reading and development.Illustrated thro
Language	English
Size	Online-Ressource (145 p)
Publisher	Taylor and Francis
Publishing place	Hoboken
Document type	Book ; Online
Note	Description based upon print version of record
ISBN	9780415508209 ; 0415508207
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Book ; Online: Cross-Curricular Teaching and Learning in the Secondary School... Mathematics

Ward-Penny, Robert / Savage, Jonathan

2010

Abstract: Cross-curricular approaches have much to offer the modern mathematics classroom. They can help teachers to present mathematics as a growing, relevant discipline that is central to much of modern life, and help learners to make sense of what they are ... ...

Abstract	Cross-curricular approaches have much to offer the modern mathematics classroom. They can help teachers to present mathematics as a growing, relevant discipline that is central to much of modern life, and help learners to make sense of what they are doing and why
Language	English
Size	Online-Ressource (169 p.)
Publisher	Taylor & Francis
Publishing place	Hoboken
Document type	Book ; Online
Note	Description based upon print version of record
ISBN	9780415572033 ; 0415572037
Database	Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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Article ; Online: Twenty-first century pathology sign-out.

Tomlins, Scott / Robinson, Daniel / Penny, Robert J / Hess, Jay L

Clinics in laboratory medicine

2012 Volume 32, Issue 4, Page(s) 639–650

Abstract: It is difficult to imagine a field that is changing as rapidly as pathology. A convergence of factors including not only scientific and technological advances but also changes in business models is transforming the field, particularly in the area of ... ...

Abstract	It is difficult to imagine a field that is changing as rapidly as pathology. A convergence of factors including not only scientific and technological advances but also changes in business models is transforming the field, particularly in the area of cancer diagnostics. The authors examine 8 themes, or "forces of change," in pathology and speculate on how these will affect pathology sign-out and the future role of pathologists in patient care.
MeSH term(s)	Humans ; Molecular Diagnostic Techniques/methods ; Pathology, Clinical/methods ; Precision Medicine/methods
Language	English
Publishing date	2012-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604580-7
ISSN	1557-9832 ; 0272-2712
ISSN (online)	1557-9832
ISSN	0272-2712
DOI	10.1016/j.cll.2012.07.002
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Article ; Online: Molecular characterization of interdigitating dendritic cell sarcoma.

Weiss, Glen J / Alarcon, Arlet / Halepota, Maqbool / Penny, Robert J / Von Hoff, Daniel D

Rare tumors

2010 Volume 2, Issue 3, Page(s) e50

Abstract: Interdigitating dendritic cell sarcoma is an extremely rare cancer that lacks a standard treatment approach. We report on a patient who was surgically resected and remains disease- free. The tumor was assessed for druggable targets using ... ...

Abstract	Interdigitating dendritic cell sarcoma is an extremely rare cancer that lacks a standard treatment approach. We report on a patient who was surgically resected and remains disease- free. The tumor was assessed for druggable targets using immunohistochemical staining to identify potential agents that could be used in the event of disease recurrence.
Language	English
Publishing date	2010-09-30
Publishing country	England
Document type	Case Reports
ZDB-ID	2514363-3
ISSN	2036-3613 ; 2036-3605
ISSN (online)	2036-3613
ISSN	2036-3605
DOI	10.4081/rt.2010.e50
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Article ; Online: Two algorithms for biospecimen comparison and differentiation using SNP genotypes.

Morris, Scott / Gel, Esma S / Smith, Jordan V / Paulauskis, Joseph D / Boom, Dirk van den / Oeth, Paul / Penny, Robert

Pharmacogenomics

2013 Volume 14, Issue 4, Page(s) 379–390

Abstract: Aims: Biobanks are frequently required to verify specimen relationships. We present two algorithms to compare SNP genotype patterns that provide an objective, high-throughput tool for verification.: Methods: The first algorithm allows for comparison ... ...

Abstract	Aims: Biobanks are frequently required to verify specimen relationships. We present two algorithms to compare SNP genotype patterns that provide an objective, high-throughput tool for verification. Methods: The first algorithm allows for comparison of all holdings within a biobank, and is well suited to construct sample relationships de novo for comparison with assumed relationships. The second algorithm is tailored to oncology, and allows one to confirm that paired DNAs from malignant and normal tissues are from the same individual in the presence of copy number variations. To evaluate both algorithms, we used an internal training data set (n = 1504) and an external validation data set (n = 1457). Results: In comparison with the results from manual review and a priori knowledge of patient relationships, we identified no errors in interpreting sample relationships within our validation data set. Conclusion: We provide an efficient and objective method of automated data analysis that is currently lacking for establishing and verifying specimen relationships in biobanks.
MeSH term(s)	Algorithms ; Biological Specimen Banks ; DNA Copy Number Variations/genetics ; Genotyping Techniques ; Humans ; Polymorphism, Single Nucleotide/genetics ; Software
Language	English
Publishing date	2013-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2019513-8
ISSN	1744-8042 ; 1462-2416
ISSN (online)	1744-8042
ISSN	1462-2416
DOI	10.2217/pgs.13.21
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Article: Evaluation and comparison of two commercially available targeted next-generation sequencing platforms to assist oncology decision making.

Weiss, Glen J / Hoff, Brandi R / Whitehead, Robert P / Sangal, Ashish / Gingrich, Susan A / Penny, Robert J / Mallery, David W / Morris, Scott M / Thompson, Eric J / Loesch, David M / Khemka, Vivek

OncoTargets and therapy

2015 Volume 8, Page(s) 959–967

Abstract: Background: It is widely acknowledged that there is value in examining cancers for genomic aberrations via next-generation sequencing (NGS). How commercially available NGS platforms compare with each other, and the clinical utility of the reported ... ...

Abstract	Background: It is widely acknowledged that there is value in examining cancers for genomic aberrations via next-generation sequencing (NGS). How commercially available NGS platforms compare with each other, and the clinical utility of the reported actionable results, are not well known. During the course of the current study, the Foundation One (F1) test generated data on a combination of somatic mutations, insertion and deletion polymorphisms, chromosomal abnormalities, and deoxyribonucleic acid (DNA) copy number changes at ~250× coverage, while the Paradigm Cancer Diagnostic (PCDx) test generated the same type of data at >5,000× coverage, plus provided messenger RNA (mRNA) expression levels. We sought to compare and evaluate paired formalin-fixed paraffin-embedded tumor tissue using these two platforms. Methods: Samples from patients with advanced solid tumors were submitted to both the F1 and PCDx vendors for NGS analysis. Turnaround time (TAT) was calculated. Biomarkers were considered clinically actionable if they had a published association with treatment response in humans and were assigned to the following categories: commercially available drug (CA), clinical trial drug (CT), or neither option (hereafter referred to as "None"). Results: The demographics of the 21 unique patient tumor samples included ten men and eleven women, with a median age of 56 years. Due to insufficient archival tissue from the same collection period, in one case, we used samples from different collections. PCDx reported first results faster than F1 in 20 cases. When received at both vendors on the same day, PCDx reported first results for 14 of 15 cases, with a median TAT of 9 days earlier than F1 (P<0.0001). Categorization of CA compared to CT and none significantly favored PCDx (P=0.012). Conclusion: In the current analysis, commercially available NGS platforms provided clinically relevant actionable targets (CA or CT) in 47%-67% of diverse cancer types. In the samples analyzed, PCDx significantly outperformed F1 in TAT, and had statistically significant higher clinically relevant actionable targets categorized as CA.
Language	English
Publishing date	2015-04-24
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2495130-4
ISSN	1178-6930
ISSN	1178-6930
DOI	10.2147/OTT.S81995
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Article ; Online: Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers.

Von Hoff, Daniel D / Stephenson, Joseph J / Rosen, Peter / Loesch, David M / Borad, Mitesh J / Anthony, Stephen / Jameson, Gayle / Brown, Susan / Cantafio, Nina / Richards, Donald A / Fitch, Tom R / Wasserman, Ernesto / Fernandez, Cristian / Green, Sylvan / Sutherland, William / Bittner, Michael / Alarcon, Arlet / Mallery, David / Penny, Robert

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2010 Volume 28, Issue 33, Page(s) 4877–4883

Abstract: Purpose: To compare the progression-free survival (PFS) using a treatment regimen selected by molecular profiling (MP) of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression (ie, patient as his own ...

Abstract	Purpose: To compare the progression-free survival (PFS) using a treatment regimen selected by molecular profiling (MP) of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression (ie, patient as his own control). Patients and methods: Patients with refractory metastatic cancer had tissue samples submitted for MP in two formats including formalin-fixed tissue for immunohistochemistry and fluorescent in situ hybridization assays and immediately frozen tissue for oligonucleotide microarray (MA) gene expression assays (all performed in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory). The MP approach was deemed of clinical benefit for the individual patient who had a PFS ratio (PFS on MP-selected therapy/PFS on prior therapy) of ≥ 1.3. Results: In 86 patients who had MP attempted, there was a molecular target detected in 84 (98%). Sixty-six of the 84 patients were treated according to MP results. Eighteen (27%) of 66 patients had a PFS ratio of ≥ 1.3 (95% CI, 17% to 38%; one-sided, one-sample P = .007). Therefore, the null hypothesis (that ≤ 15% of this patient population would have a PFS ratio of ≥ 1.3) was rejected. Conclusion: It is possible to identify molecular targets in patients' tumors from nine different centers across the United States. In 27% of patients, the MP approach resulted in a longer PFS on an MP-suggested regimen than on the regimen on which the patient had just experienced progression. Issues to be considered in interpretation of this study include limited prior experience with patients as their own controls as a study end point and overall patient attrition.
MeSH term(s)	Adult ; Aged ; Disease-Free Survival ; Female ; Gene Expression Profiling ; Humans ; Male ; Middle Aged ; Neoplasms/metabolism ; Neoplasms/mortality ; Neoplasms/therapy ; Pilot Projects
Language	English
Publishing date	2010-11-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2009.26.5983
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The somatic genomic landscape of glioblastoma.

Brennan, Cameron W / Verhaak, Roel G W / McKenna, Aaron / Campos, Benito / Noushmehr, Houtan / Salama, Sofie R / Zheng, Siyuan / Chakravarty, Debyani / Sanborn, J Zachary / Berman, Samuel H / Beroukhim, Rameen / Bernard, Brady / Wu, Chang-Jiun / Genovese, Giannicola / Shmulevich, Ilya / Barnholtz-Sloan, Jill / Zou, Lihua / Vegesna, Rahulsimham / Shukla, Sachet A /

Ciriello, Giovanni / Yung, W K / Zhang, Wei / Sougnez, Carrie / Mikkelsen, Tom / Aldape, Kenneth / Bigner, Darell D / Van Meir, Erwin G / Prados, Michael / Sloan, Andrew / Black, Keith L / Eschbacher, Jennifer / Finocchiaro, Gaetano / Friedman, William / Andrews, David W / Guha, Abhijit / Iacocca, Mary / O'Neill, Brian P / Foltz, Greg / Myers, Jerome / Weisenberger, Daniel J / Penny, Robert / Kucherlapati, Raju / Perou, Charles M / Hayes, D Neil / Gibbs, Richard / Marra, Marco / Mills, Gordon B / Lander, Eric / Spellman, Paul / Wilson, Richard / Sander, Chris / Weinstein, John / Meyerson, Matthew / Gabriel, Stacey / Laird, Peter W / Haussler, David / Getz, Gad / Chin, Lynda

Cell

2013 Volume 155, Issue 2, Page(s) 462–477

Abstract: We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature ... ...

Abstract	We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.
MeSH term(s)	Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Female ; Gene Expression Profiling ; Gene Regulatory Networks ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Humans ; Male ; Mutation ; Proteome/analysis ; Signal Transduction
Chemical Substances	Proteome
Language	English
Publishing date	2013-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2013.09.034
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Article: Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Abeshouse, Adam / Adebamowo, Clement / Adebamowo, Sally N / Akbani, Rehan / Akeredolu, Teniola / Ally, Adrian / Anderson, Matthew L / Anur, Pavana / Appelbaum, Elizabeth L / Armenia, Joshua / Auman, J. Todd / Bailey, Matthew H / Baker, Laurence / Balasundaram, Miruna / Balu, Saianand / Barthel, Floris P / Bartlett, John / Baylin, Stephen B / Behera, Madhusmita /

Belyaev, Dmitry / Bennett, Joesph / Benz, Christopher / Beroukhim, Rameen / Birrer, Michael / Bocklage, Thèrése / Bodenheimer, Tom / Boice, Lori / Bootwalla, Moiz S / Bowen, Jay / Bowlby, Reanne / Boyd, Jeff / Brohl, Andrew S / Brooks, Denise / Byers, Lauren / Carlsen, Rebecca / Castro, Patricia / Chen, Hsiao-Wei / Cherniack, Andrew D / Chibon, Fréderic / Chin, Lynda / Cho, Juok / Chuah, Eric / Chudamani, Sudha / Cibulskis, Carrie / Cooper, Lee A.D / Cope, Leslie / Cordes, Matthew G / Crain, Daniel / Curley, Erin / Danilova, Ludmila / Dao, Fanny / Davis, Ian J / Davis, Lara E / Defreitas, Timothy / Delman, Keith / Demchok, John A / Demetri, George D / Demicco, Elizabeth G / Dhalla, Noreen / Diao, Lixia / Ding, Li / DiSaia, Phil / Dottino, Peter / Doyle, Leona A / Drill, Esther / Dubina, Michael / Eschbacher, Jennifer / Fedosenko, Konstantin / Felau, Ina / Ferguson, Martin L / Frazer, Scott / Fronick, Catrina C / Fulidou, Victoria / Fulton, Lucinda A / Fulton, Robert S / Gabriel, Stacey B / Gao, Jianjiong / Gao, Qingsong / Gardner, Johanna / Gastier-Foster, Julie M / Gay, Carl M / Gehlenborg, Nils / Gerken, Mark / Getz, Gad / Godwin, Andrew K / Godwin, Eryn M / Gordienko, Elena / Grilley-Olson, Juneko E / Gutman, David A / Gutmann, David H / Hayes, D. Neil / Hegde, Apurva M / Heiman, David I / Heins, Zachary / Helsel, Carmen / Hepperla, Austin J / Higgins, Kelly / Hoadley, Katherine A / Hobensack, Shital / Holt, Robert A / Hoon, Dave B / Hornick, Jason L / Hoyle, Alan P / Hu, Xin / Huang, Mei / Hutter, Carolyn M / Iacocca, Mary / Ingram, Davis R / Ittmann, Michael / Iype, Lisa / Jefferys, Stuart R / Jones, Kevin B / Jones, Corbin D / Jones, Steven J.M / Kalir, Tamara / Karlan, Beth Y / Karseladze, Apollon / Kasaian, Katayoon / Kim, Jaegil / Kundra, Ritika / Kuo, Hanluen / Ladanyi, Marc / Lai, Phillip H / Laird, Peter W / Larsson, Erik / Lawrence, Michael S / Lazar, Alexander J / Lee, Sanghoon / Lee, Darlene / Lehmann, Kjong-Van / Leraas, Kristen M / Lester, Jenny / Levine, Douglas A / Li, Irene / Lichtenberg, Tara M / Lin, Pei / Liu, Jia / Liu, Wenbin / Liu, Eric Minwei / Lolla, Laxmi / Lu, Yiling / Ma, Yussanne / Madan, Rashna / Maglinte, Dennis T / Magliocco, Anthony / Maki, Robert G / Mallery, David / Manikhas, Georgy / Mardis, Elaine R / Mariamidze, Armaz / Marra, Marco A / Martignetti, John A / Martinez, Cathleen / Mayo, Michael / McLellan, Michael D / Meier, Sam / Meng, Shaowu / Meyerson, Matthew / Mieczkowski, Piotr A / Miller, Christopher A / Mills, Gordon B / Moore, Richard A / Morris, Scott / Mose, Lisle E / Mozgovoy, Evgeny / Mungall, Andrew J / Mungall, Karen / Nalisnik, Michael / Naresh, Rashi / Newton, Yulia / Noble, Michael S / Novak, Janet E / Ochoa, Angelica / Olvera, Narciso / Owonikoko, Taofeek K / Paklina, Oxana / Parfitt, Jeremy / Parker, Joel S / Pastore, Alessandro / Paulauskis, Joseph / Penny, Robert / Pereira, Elena / Perou, Charles M / Perou, Amy H / Pihl, Todd / Pollock, Raphael E / Potapova, Olga / Radenbaugh, Amie J / Ramalingam, Suresh S / Ramirez, Nilsa C / Rathmell, W. Kimryn / Raut, Chandrajit P / Riedel, Richard F / Reilly, Colleen / Reynolds, Sheila M / Roach, Jeffrey / Robertson, A. Gordon / Roszik, Jason / Rubin, Brian P / Sadeghi, Sara / Saksena, Gordon / Salner, Andrew / Sanchez-Vega, Francisco / Sander, Chris / Schein, Jacqueline E / Schmidt, Heather K / Schultz, Nikolaus / Schumacher, Steven E / Sekhon, Harman / Senbabaoglu, Yasin / Setdikova, Galiya / Shelton, Candace / Shelton, Troy / Shen, Ronglai / Shi, Yan / Shih, Juliann / Shmulevich, Ilya / Sica, Gabriel L / Simons, Janae V / Singer, Samuel / Sipahimalani, Payal / Skelly, Tara / Socci, Nicholas / Sofia, Heidi J / Soloway, Matthew G / Spellman, Paul / Sun, Qiang / Swanson, Patricia / Tam, Angela / Tan, Donghui / Tarnuzzer, Roy / Thiessen, Nina / Thompson, Eric / Thorne, Leigh B / Tong, Pan / Torres, Keila E / van de Rijn, Matt / Van Den Berg, David J / Van Tine, Brian A / Veluvolu, Umadevi / Verhaak, Roel / Voet, Doug / Voronina, Olga / Wan, Yunhu / Wang, Zhining / Wang, Jing / Weinstein, John N / Weisenberger, Daniel J / Wilkerson, Matthew D / Wilson, Richard K / Wise, Lisa / Wong, Tina / Wong, Winghing / Wrangle, John / Wu, Ye / Wyczalkowski, Matthew / Yang, Liming / Yau, Christina / Yellapantula, Venkata / Zenklusen, Jean C / Zhang, Jiashan (Julia) / Zhang, Hailei / Zhang, Hongxin / Zmuda, Erik

Cell. 2017 Nov. 02, v. 171, no. 4

2017

Abstract: Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the ... ...

Institution	The Cancer Genome Atlas Research Network
Abstract	Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.
Keywords	DNA methylation ; adults ; clinical trials ; epithelium ; genes ; genomics ; histology ; messenger RNA ; patients ; sarcoma ; therapeutics
Language	English
Dates of publication	2017-1102
Size	p. 950-965.e28.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2017.10.014
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

Linehan, W Marston / Spellman, Paul T / Ricketts, Christopher J / Creighton, Chad J / Fei, Suzanne S / Davis, Caleb / Wheeler, David A / Murray, Bradley A / Schmidt, Laura / Vocke, Cathy D / Peto, Myron / Al Mamun, Abu Amar M / Shinbrot, Eve / Sethi, Anurag / Brooks, Samira / Rathmell, W Kimryn / Brooks, Angela N / Hoadley, Katherine A / Robertson, A Gordon /

Brooks, Denise / Bowlby, Reanne / Sadeghi, Sara / Shen, Hui / Weisenberger, Daniel J / Bootwalla, Moiz / Baylin, Stephen B / Laird, Peter W / Cherniack, Andrew D / Saksena, Gordon / Haake, Scott / Li, Jun / Liang, Han / Lu, Yiling / Mills, Gordon B / Akbani, Rehan / Leiserson, Mark D M / Raphael, Benjamin J / Anur, Pavana / Bottaro, Donald / Albiges, Laurence / Barnabas, Nandita / Choueiri, Toni K / Czerniak, Bogdan / Godwin, Andrew K / Hakimi, A Ari / Ho, Thai H / Hsieh, James / Ittmann, Michael / Kim, William Y / Krishnan, Bhavani / Merino, Maria J / Mills Shaw, Kenna R / Reuter, Victor E / Reznik, Ed / Shelley, Carl S / Shuch, Brian / Signoretti, Sabina / Srinivasan, Ramaprasad / Tamboli, Pheroze / Thomas, George / Tickoo, Satish / Burnett, Kenneth / Crain, Daniel / Gardner, Johanna / Lau, Kevin / Mallery, David / Morris, Scott / Paulauskis, Joseph D / Penny, Robert J / Shelton, Candace / Shelton, W Troy / Sherman, Mark / Thompson, Eric / Yena, Peggy / Avedon, Melissa T / Bowen, Jay / Gastier-Foster, Julie M / Gerken, Mark / Leraas, Kristen M / Lichtenberg, Tara M / Ramirez, Nilsa C / Santos, Tracie / Wise, Lisa / Zmuda, Erik / Demchok, John A / Felau, Ina / Hutter, Carolyn M / Sheth, Margi / Sofia, Heidi J / Tarnuzzer, Roy / Wang, Zhining / Yang, Liming / Zenklusen, Jean C / Zhang, Jiashan / Ayala, Brenda / Baboud, Julien / Chudamani, Sudha / Liu, Jia / Lolla, Laxmi / Naresh, Rashi / Pihl, Todd / Sun, Qiang / Wan, Yunhu / Wu, Ye / Ally, Adrian / Balasundaram, Miruna / Balu, Saianand / Beroukhim, Rameen / Bodenheimer, Tom / Buhay, Christian / Butterfield, Yaron S N / Carlsen, Rebecca / Carter, Scott L / Chao, Hsu / Chuah, Eric / Clarke, Amanda / Covington, Kyle R / Dahdouli, Mahmoud / Dewal, Ninad / Dhalla, Noreen / Doddapaneni, Harsha V / Drummond, Jennifer A / Gabriel, Stacey B / Gibbs, Richard A / Guin, Ranabir / Hale, Walker / Hawes, Alicia / Hayes, D Neil / Holt, Robert A / Hoyle, Alan P / Jefferys, Stuart R / Jones, Steven J M / Jones, Corbin D / Kalra, Divya / Kovar, Christie / Lewis, Lora / Li, Jie / Ma, Yussanne / Marra, Marco A / Mayo, Michael / Meng, Shaowu / Meyerson, Matthew / Mieczkowski, Piotr A / Moore, Richard A / Morton, Donna / Mose, Lisle E / Mungall, Andrew J / Muzny, Donna / Parker, Joel S / Perou, Charles M / Roach, Jeffrey / Schein, Jacqueline E / Schumacher, Steven E / Shi, Yan / Simons, Janae V / Sipahimalani, Payal / Skelly, Tara / Soloway, Matthew G / Sougnez, Carrie / Tam, Angela / Tan, Donghui / Thiessen, Nina / Veluvolu, Umadevi / Wang, Min / Wilkerson, Matthew D / Wong, Tina / Wu, Junyuan / Xi, Liu / Zhou, Jane / Bedford, Jason / Chen, Fengju / Fu, Yao / Gerstein, Mark / Haussler, David / Kasaian, Katayoon / Lai, Phillip / Ling, Shiyun / Radenbaugh, Amie / Van Den Berg, David / Weinstein, John N / Zhu, Jingchun / Albert, Monique / Alexopoulou, Iakovina / Andersen, Jeremiah J / Auman, J Todd / Bartlett, John / Bastacky, Sheldon / Bergsten, Julie / Blute, Michael L / Boice, Lori / Bollag, Roni J / Boyd, Jeff / Castle, Erik / Chen, Ying-Bei / Cheville, John C / Curley, Erin / Davies, Benjamin / DeVolk, April / Dhir, Rajiv / Dike, Laura / Eckman, John / Engel, Jay / Harr, Jodi / Hrebinko, Ronald / Huang, Mei / Huelsenbeck-Dill, Lori / Iacocca, Mary / Jacobs, Bruce / Lobis, Michael / Maranchie, Jodi K / McMeekin, Scott / Myers, Jerome / Nelson, Joel / Parfitt, Jeremy / Parwani, Anil / Petrelli, Nicholas / Rabeno, Brenda / Roy, Somak / Salner, Andrew L / Slaton, Joel / Stanton, Melissa / Thompson, R Houston / Thorne, Leigh / Tucker, Kelinda / Weinberger, Paul M / Winemiller, Cynthia / Zach, Leigh Anne / Zuna, Rosemary

The New England journal of medicine

2016 Volume 374, Issue 2, Page(s) 135–145

Abstract: Background: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors ... ...

Abstract	Background: Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. Methods: We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Results: Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Conclusions: Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).
MeSH term(s)	Carcinoma, Papillary/genetics ; Carcinoma, Papillary/metabolism ; CpG Islands/physiology ; DNA Methylation ; Humans ; Kidney Neoplasms/genetics ; Kidney Neoplasms/metabolism ; MicroRNAs/chemistry ; Mutation ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; Phenotype ; Proto-Oncogene Proteins c-met/chemistry ; Proto-Oncogene Proteins c-met/genetics ; Proto-Oncogene Proteins c-met/metabolism ; RNA, Messenger/chemistry ; RNA, Neoplasm/chemistry ; Sequence Analysis, RNA ; Signal Transduction/physiology
Chemical Substances	MicroRNAs ; NF-E2-Related Factor 2 ; NFE2L2 protein, human ; RNA, Messenger ; RNA, Neoplasm ; MET protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-met (EC 2.7.10.1)
Language	English
Publishing date	2016-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMoa1505917
Database	MEDical Literature Analysis and Retrieval System OnLINE

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