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Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

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

  2. Author Address

    NCI, Canc Genome Atlas Program Off, Ctr Dr, NIH, Bldg 31,Suite 3A20, Bethesda, MD 20892 USA.Washington Univ, McDonnell Genome Inst, St Louis, MO 63108 USA.Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02114 USA.Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.Harvard Med Sch, Boston, MA 02114 USA.MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02142 USA.Harvard Univ, Cambridge, MA 02142 USA.Univ Calif Santa Cruz, Genom Inst, Santa Cruz, CA 95064 USA.Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA.Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.Univ N Carolina, Dept Genet, Sch Med, Chapel Hill, NC 27599 USA.Univ N Carolina, Lineberger Comprehens Canc Ctr, Sch Med, Chapel Hill, NC 27599 USA.Univ N Carolina, Dept Internal Med, Div Med Oncol, Sch Med, Chapel Hill, NC 27599 USA.Univ N Carolina, Dept Pathol, Sch Med, Chapel Hill, NC 27599 USA.Univ N Carolina, Lab Med, Sch Med, Chapel Hill, NC 27599 USA.Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.Univ N Carolina, Res Comp Ctr, Chapel Hill, NC 27599 USA.Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA.H Lee Moffitt Canc Ctr & Res Inst, Sarcoma Dept, Tampa, FL 33612 USA.Canadas Michael Smith Genome Sci Ctr, BC Canc Agcy, Vancouver, BC V5Z 4S6, Canada.Jackson Lab Genom Med, Farmington, CT 06032 USA.Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.Harbor Med Sch, Dept Med, Boston, MA 02215 USA.Harbor Med Sch, Dept Pathol, Boston, MA 02215 USA.Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA.Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.Van Andel Res Inst, Ctr Epigenet, Grand Rapids, MI 49503 USA.Med Univ South Carolina, Dept Med, Div Hematol Oncol, Charleston, SC 29425 USA.Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA.Inst Syst Biol, Seattle, WA 98109 USA.Buck Inst Res Aging, Novato, CA 94945 USA.Mem Sloan Kettering Canc Ctr, Ctr Mol Oncol, New York, NY 10065 USA.Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA.Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncology, Houston, TX 77030 USA.Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97239 USA.Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA.Harvard Med Sch, Ctr Biomed Informat, Boston, MA 02115 USA.Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.Emory Univ, Atlanta, GA 30322 USA.Nationwide Childrens Hosp, Res Inst, Columbus, OH 43205 USA.Ohio State Univ, Columbus, OH 43210 USA.Baylor Coll Med, Houston, TX 77030 USA.Botkin City Hosp, Moscow 125284, Russia.AV Vishnevskiy Inst Surg, Moscow, Russia.Brigham & Womens Hosp, Dept Surg, Harvard Med Sch, Boston, MA 02115 USA.Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.Harvard Med Sch, Boston, MA 02215 USA.Cedars Sinai Med Ctr, Womens Canc Program, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA.Cureline Inc, San Francisco, CA 94080 USA.Sarcoma Ctr, Dana Farber Canc Inst, Boston, MA 02215 USA.Ludwig Ctr Harvard, Havard Med Sch, Boston, MA 02215 USA.Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.Hartford Hosp, Gray Canc Ctr, Hartford, CT 06102 USA.Helen F Graham Canc Ctr, Newark, DE 19713 USA.Res Inst, Newark, DE 19713 USA.Icahn Sch Med Mt Sinai, Dept Obstet Gynecol & Reprod Sci, New York, NY 10029 USA.Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA.Inst Human Virol, Abuja, Nigeria.Int Genom Consortium, Phoenix, AZ 85004 USA.John Wayne Canc Inst, Santa Monica, CA 90025 USA.London Hlth Sci Ctr, Ontario Tumour Bank, London Site, London, ON, Canada.Massachusetts Gen Hosp, Boston, MA 02114 USA.NN Blokhin Russian Canc Res Ctr, Moscow 115478, Russia.Natl Canc Ctr Georgia, Tbilisi, Rep of Georgia.NYU, Langone Med Ctr, Perlmutter Canc Ctr, New York, NY 10016 USA.Northwell Hlth, Monter Canc Ctr, New Hyde Pk, NY 11042 USA.Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA.Ontario Inst Canc Res, Ontario Tumour Bank, Toronto, ON M5G 0A3, Canada.St Josephs Hosp, Phoenix, AZ 85013 USA.St Petersburg Acad Univ, St Petersburg 194021, Russia.St Petersburg City Oncol Clin, St Petersburg 198255, Russia.Ottawa Hosp, Ontario Tumour Bank, Ottawa site, Ottawa, ON K1H 8L6, Canada.Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA.Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Orange, CA 92868 USA.Univ Kansas, Med Ctr, Kansas City, KS 66160 USA.Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.Univ Maryland, Sch Med, Greenebaum Comprehens Canc Ctr, Baltimore, MD 21201 USA.Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Pathol, Albuquerque, NM 87131 USA.Univ New Mexico, Hlth Sci Ctr, Sch Med, Human Tissue Repository,Dept Pathol, Albuquerque, NM 87131 USA.Univ North Carolina Chapel Hill, Chapel Hill, NC 27599 USA.Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA.Univ North Carolina Chapel Hill, Sch Med, Urol Oncol Program, Canc Genet,Clin Res, Chapel Hill, NC 27599 USA.Washington Univ, Dept Neurol, St Louis, MO 63110 USA.Leidos Biomed Res, Rockville, MD 20850 USA.Leidos Biomed Res, Gaithersburg, MD 20877 USA.CSRA Incorporated, Falls Church, VA 22042 USA.NCI, Bethesda, MD 20892 USA.MLF Consulting, Arlington, MA USA.NHGRI, NIH, Bethesda, MD 20892 USA.Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.Cleveland Clin, Robert J Tomsich Pathol and Lab Med Inst, Cleveland, OH 44195 USA.Cleveland Clin, Dept Canc Biol, Cleveland, OH 44195 USA.Cleveland Clin, Lerner Res Inst, Cleveland, OH 44195 USA.Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA.Univ Michigan, Ann Arbor, MI 48109 USA.Duke Univ, Med Ctr, Dept Med, Div Med Oncol, Durham, NC 27710 USA.Washington Univ, Dept Med, St Louis, MO 63110 USA.Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10065 USA.Washington Univ, Med Oncol, St Louis, MO 63110 USA.Ohio State Univ, Dept Surg, Div Surg Oncol, Columbus, OH 43210 USA.Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA.Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA.Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA.INSERM, U1218, F-33076 Bordeaux, France.
    1. Year: 2017
    2. Date: Nov 02
  2. Journal: Cell
  3. CELL PRESS,
    1. 171
    2. 4
    3. Pages: 950-965
  5. Type of Article: Article
  6. ISSN: 0092-8674
  1. 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.

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  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.cell.2017.10.014
  3. PMID: 29100075
  4. PMCID: PMC5693358
  5. View record in Web of Science®
  6. WOS: 000414250900021

Library Notes

  1. Fiscal Year: FY2017-2018
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