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Proteomics, Post-translational Modifications, and Integrative Analyses Reveal Molecular Heterogeneity within Medulloblastoma Subgroups.
Archer, Tenley C; Ehrenberger, Tobias; Mundt, Filip; Gold, Maxwell P; Krug, Karsten; Mah, Clarence K; Mahoney, Elizabeth L; Daniel, Colin J; LeNail, Alexander; Ramamoorthy, Divya; Mertins, Philipp; Mani, D R; Zhang, Hailei; Gillette, Michael A; Clauser, Karl; Noble, Michael; Tang, Lauren C; Pierre-François, Jessica; Silterra, Jacob; Jensen, James; Tamayo, Pablo; Korshunov, Andrey; Pfister, Stefan M; Kool, Marcel; Northcott, Paul A; Sears, Rosalie C; Lipton, Jonathan O; Carr, Steven A; Mesirov, Jill P; Pomeroy, Scott L; Fraenkel, Ernest.
Afiliación
  • Archer TC; Department of Neurology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ehrenberger T; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Mundt F; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
  • Gold MP; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Krug K; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mah CK; Department of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA.
  • Mahoney EL; Department of Neurology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Daniel CJ; Department of Molecular and Medical Genetics, Oregon Health and Science University (OHSU), Portland, OR, USA.
  • LeNail A; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Ramamoorthy D; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
  • Mertins P; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Mani DR; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Zhang H; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gillette MA; Harvard Medical School, Boston, MA, USA; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital (MGH), Boston, MA, USA.
  • Clauser K; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Noble M; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Tang LC; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Pierre-François J; Department of Neurology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
  • Silterra J; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Jensen J; Department of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA.
  • Tamayo P; Department of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California San Diego (UCSD), La Jolla, CA, USA.
  • Korshunov A; CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Neuropathology, Heidelberg University, Heidelberg, Germany.
  • Pfister SM; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germ
  • Kool M; Hopp Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Northcott PA; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany; Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
  • Sears RC; Department of Molecular and Medical Genetics, Oregon Health and Science University (OHSU), Portland, OR, USA.
  • Lipton JO; Department of Neurology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
  • Carr SA; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: scarr@broadinstitute.org.
  • Mesirov JP; Department of Medicine, University of California San Diego (UCSD), La Jolla, CA, USA; Moores Cancer Center, University of California San Diego (UCSD), La Jolla, CA, USA. Electronic address: jmesirov@ucsd.edu.
  • Pomeroy SL; Department of Neurology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: scott.pomeroy@childrens.harvard.edu.
  • Fraenkel E; Eli and Edythe Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. Electronic address: fraenkel-admin@mit.edu.
Cancer Cell ; 34(3): 396-410.e8, 2018 09 10.
Article en En | MEDLINE | ID: mdl-30205044
ABSTRACT
There is a pressing need to identify therapeutic targets in tumors with low mutation rates such as the malignant pediatric brain tumor medulloblastoma. To address this challenge, we quantitatively profiled global proteomes and phospho-proteomes of 45 medulloblastoma samples. Integrated analyses revealed that tumors with similar RNA expression vary extensively at the post-transcriptional and post-translational levels. We identified distinct pathways associated with two subsets of SHH tumors, and found post-translational modifications of MYC that are associated with poor outcomes in group 3 tumors. We found kinases associated with subtypes and showed that inhibiting PRKDC sensitizes MYC-driven cells to radiation. Our study shows that proteomics enables a more comprehensive, functional readout, providing a foundation for future therapeutic strategies.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Biomarcadores de Tumor / Procesamiento Proteico-Postraduccional / Meduloblastoma Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Biomarcadores de Tumor / Procesamiento Proteico-Postraduccional / Meduloblastoma Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos