Advances in sarcoma genomics and new therapeutic targets
Barry S. Taylor,Jordi Barretina,Jordi Barretina,Robert G. Maki,Cristina R. Antonescu,Samuel Singer,Marc Ladanyi +6 more
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TLDR
The core molecular determinants of sarcomagenesis are discussed and the emerging genomic and functional genetic approaches that, coupled with novel therapeutic strategies, have the potential to transform the care of patients with sarcoma are emphasized.Abstract:
Increasingly, human mesenchymal malignancies are being classified by the abnormalities that drive their pathogenesis. Although many of these aberrations are highly prevalent within particular sarcoma subtypes, few are currently targeted therapeutically. Indeed, most subtypes of sarcoma are still treated with traditional therapeutic modalities, and in many cases sarcomas are resistant to adjuvant therapies. In this Review, we discuss the core molecular determinants of sarcomagenesis and emphasize the emerging genomic and functional genetic approaches that, coupled with novel therapeutic strategies, have the potential to transform the care of patients with sarcoma.read more
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Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas
Adam Abeshouse,Clement Adebamowo,Sally N. Adebamowo,Rehan Akbani,Teniola Akeredolu,Adrian Ally,Matthew L. Anderson,Pavana Anur,Elizabeth L. Appelbaum,Joshua Armenia,J. Todd Auman,Matthew A. Bailey,Laurence H. Baker,Miruna Balasundaram,Saianand Balu,Floris P. Barthel,John Bartlett,Stephen B. Baylin,Madhusmita Behera,Dmitry Belyaev,Joesph Bennett,Christopher C. Benz,Rameen Beroukhim,Michael J. Birrer,Therese Bocklage,Tom Bodenheimer,Lori Boice,Moiz S. Bootwalla,Jay Bowen,Reanne Bowlby,Jeff Boyd,Andrew S. Brohl,Denise Brooks,Lauren Averett Byers,Rebecca Carlsen,Patricia Castro,Hsiao-Wei Chen,Andrew D. Cherniack,Frédéric Chibon,Lynda Chin,Juok Cho,Eric Chuah,Sudha Chudamani,Carrie Cibulskis,Lee Cooper,Leslie Cope,Matthew G. Cordes,Daniel Crain,Erin Curley,Ludmila Danilova,Fanny Dao,Ian J. Davis,Lara E. Davis,Timothy Defreitas,Keith A. Delman,John A. Demchok,George D. Demetri,Elizabeth G. Demicco,Noreen Dhalla,Lixia Diao,Li Ding,Phil DiSaia,Peter Dottino,Leona A. Doyle,Esther Drill,Michael Dubina,Jennifer M. Eschbacher,Konstantin V. Fedosenko,Ina Felau,Martin L. Ferguson,Scott Frazer,Catrina Fronick,Victoria Fulidou,Lucinda Fulton,Robert S. Fulton,Stacey Gabriel,Jianjiong Gao,Qingsong Gao,Johanna Gardner,Julie M. Gastier-Foster,Nils Gehlenborg,Mark Gerken,Gad Getz,Andrew K. Godwin,Eryn M. Godwin,Elena Gordienko,Juneko E. Grilley-Olson,David A. Gutman,David H. Gutmann,D. Neil Hayes,Apurva M. Hegde,David I. Heiman,Zachary J. Heins,Carmen Helsel,Austin J. Hepperla,Kelly Higgins,Katherine A. Hoadley,Shital Hobensack,Robert A. Holt,Dave B. Hoon,Jason L. Hornick,Alan P. Hoyle,Xin Hu,Mei Huang,Carolyn M. Hutter,Mary Iacocca,Davis R. Ingram,Michael Ittmann,Lisa Iype,Stuart R. Jefferys,Kevin B. Jones,Corbin D. Jones,Steven J.M. Jones,Tamara Kalir,Beth Y. Karlan,Apollon Karseladze,Katayoon Kasaian,Jaegil Kim,Ritika Kundra,Hanluen Kuo,Marc Ladanyi,Phillip H. Lai,Peter W. Laird,Erik G. Larsson,Michael S. Lawrence,Alexander J. Lazar,Sanghoon Lee,Darlene Lee,Kjong-Van Lehmann,Kristen M. Leraas,Jenny Lester,Douglas A. Levine,Irene Li,Tara M. Lichtenberg,Pei Lin,Jia Liu,Wen-Bin Liu,Eric Minwei Liu,Laxmi Lolla,Yiling Lu,Yussanne Ma,Rashna Madan,Dennis T. Maglinte,Anthony M. Magliocco,Robert G. Maki,David Mallery,Georgy Manikhas,Elaine R. Mardis,Armaz Mariamidze,Marco A. Marra,John A. Martignetti,Cathleen Martinez,Michael Mayo,Michael D. McLellan,Sam Meier,Shaowu Meng,Matthew Meyerson,Piotr A. Mieczkowski,Christopher A. Miller,Gordon B. Mills,Richard A. Moore,Scott Morris,Lisle E. Mose,Evgeny Mozgovoy,Andrew J. Mungall,Karen Mungall,Michael Nalisnik,Rashi Naresh,Yulia Newton,Michael S. Noble,Janet E. Novak,Angelica Ochoa,Narciso Olvera,Taofeek K. Owonikoko,Oxana Paklina,Jeremy Parfitt,Joel S. Parker,Alessandro Pastore,Joseph Paulauskis,Robert Penny,Elena Pereira,Charles M. Perou,Amy H. Perou,Todd Pihl,Raphael E. Pollock,Olga Potapova,Amie Radenbaugh,Suresh S. Ramalingam,Nilsa C. Ramirez,W. Kimryn Rathmell,Chandrajit P. Raut,Richard F. Riedel,Colleen Reilly,Sheila Reynolds,Jeffrey Roach,A. Gordon Robertson,Jason Roszik,Brian P. Rubin,Sara Sadeghi,Gordon Saksena,Andrew Salner,Francisco Sanchez-Vega,Chris Sander,Jacqueline E. Schein,Heather Schmidt,Nikolaus Schultz,Steven E. Schumacher,Harman Sekhon,Yasin Senbabaoglu,Galiya Setdikova,Candace Shelton,Troy Shelton,Ronglai Shen,Yan Shi,Juliann Shih,Ilya Shmulevich,Gabriel Sica,Janae V. Simons,Samuel Singer,Payal Sipahimalani,Tara Skelly,Nicholas D. Socci,Heidi J. Sofia,Matthew G. Soloway,Paul T. Spellman,Qiang Sun,Patricia Swanson,Angela Tam,Donghui Tan,Roy Tarnuzzer,Nina Thiessen,Eric M. Thompson,Leigh B. Thorne,Pan Tong,Keila E. Torres,Matt van de Rijn,David Van Den Berg,Brian A. Van Tine,Umadevi Veluvolu,Roel G.W. Verhaak,Doug Voet,Olga Voronina,Yunhu Wan,Zhining Wang,Jing Wang,John N. Weinstein,Daniel J. Weisenberger,Matthew D. Wilkerson,Richard K. Wilson,Lisa Wise,Tina Wong,Wing Hing Wong,John Wrangle,Ye Wu,Matthew A. Wyczalkowski,Liming Yang,Christina Yau,Venkata Yellapantula,Jean C. Zenklusen,Jiashan Zhang,Hailei Zhang,Hongxin Zhang,Erik Zmuda +262 more
TL;DR: This large-scale analysis of 206 adult soft tissue sarcomas 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.
Journal ArticleDOI
PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors
William Lee,Sewit Teckie,Thomas Wiesner,Leili Ran,Carlos N. Prieto Granada,Mingyan Lin,Sinan Zhu,Zhen Cao,Yupu Liang,Andrea Sboner,William D. Tap,Jonathan A. Fletcher,Kety Huberman,Li-Xuan Qin,Agnes Viale,Samuel Singer,Deyou Zheng,Michael F. Berger,Yu Chen,Cristina R. Antonescu,Ping Chi +20 more
TL;DR: The highly recurrent and specific inactivation of PRC2 components, NF1 and CDKN2A highlights their critical and potentially cooperative roles in MPNST pathogenesis.
Journal ArticleDOI
Recent advances in osteosarcoma.
TL;DR: An overview of current clinical trials which largely focus on stimulation of the immune system or rely on the inhibition of kinases such as Src and mTOR is presented and a case is made for individualized treatment of OS patients, based on interdisciplinary cooperation in dedicated Sarcoma Centers.
Journal ArticleDOI
Hypoxia-Dependent Modification of Collagen Networks Promotes Sarcoma Metastasis
T.S. Karin Eisinger-Mathason,Minsi Zhang,Qiong Qiu,Nicolas Skuli,Michael S. Nakazawa,Tatiana A. Karakasheva,Vera Mucaj,Jessica E.S. Shay,Lars Stangenberg,Navid Sadri,Ellen Puré,Sam S. Yoon,David G. Kirsch,M. Celeste Simon +13 more
TL;DR: The potential use of a novel therapeutic target for the treatment of metastatic UPS, specifi cally the collagen-modifying enzyme PLOD2 is shown, and successful inhibition of this enzyme may reduce tumor cell dissemination.
Journal ArticleDOI
Clinical implications of intratumor heterogeneity: challenges and opportunities
Santiago Ramón y Cajal,Marta Sesé,Claudia Capdevila,Claudia Capdevila,Trond Aasen,Leticia De Mattos-Arruda,Salvador J. Diaz-Cano,Javier Hernández-Losa,Josep Castellví +8 more
TL;DR: The role of intratumoral heterogeneity is highlighted, focusing on the clinical and biological ramifications this phenomenon poses, and how understanding the involved drivers and functional consequences can provide novel insight needed to confront the problem of therapeutic resistance in tumors.
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