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Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma.
Zomerman, Walderik W; Plasschaert, Sabine L A; Conroy, Siobhan; Scherpen, Frank J; Meeuwsen-de Boer, Tiny G J; Lourens, Harm J; Guerrero Llobet, Sergi; Smit, Marlinde J; Slagter-Menkema, Lorian; Seitz, Annika; Gidding, Corrie E M; Hulleman, Esther; Wesseling, Pieter; Meijer, Lisethe; van Kempen, Leon C; van den Berg, Anke; Warmerdam, Daniël O; Kruyt, Frank A E; Foijer, Floris; van Vugt, Marcel A T M; den Dunnen, Wilfred F A; Hoving, Eelco W; Guryev, Victor; de Bont, Eveline S J M; Bruggeman, Sophia W M.
Afiliação
  • Zomerman WW; Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Plasschaert SLA; Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; Princess Máxima Center for Pediatric Oncology, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
  • Conroy S; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Scherpen FJ; Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Meeuwsen-de Boer TGJ; Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Lourens HJ; Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Guerrero Llobet S; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Smit MJ; Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Slagter-Menkema L; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; Department of Otorhinolaryngology/Head and Neck Surgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Gr
  • Seitz A; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Gidding CEM; Department of Pediatric Oncology/Pediatrics, Radboud University Medical Center Nijmegen, Geert Groteplein Zuid 10, 6525 HB Nijmegen, the Netherlands.
  • Hulleman E; Department of Pediatric Oncology/Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
  • Wesseling P; Princess Máxima Center for Pediatric Oncology, Lundlaan 6, 3584 EA Utrecht, the Netherlands; Department of Pathology, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands.
  • Meijer L; Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • van Kempen LC; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; Department of Pathology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
  • van den Berg A; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Warmerdam DO; iPSC CRISPR Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Kruyt FAE; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Foijer F; iPSC CRISPR Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; ERIBA, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • van Vugt MATM; Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • den Dunnen WFA; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Hoving EW; Department of Neurosurgery, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; Princess Máxima Center for Pediatric Oncology, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
  • Guryev V; ERIBA, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • de Bont ESJM; Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
  • Bruggeman SWM; Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands. Electronic address: s.w.m.bruggeman@umcg.nl.
Cell Rep ; 22(12): 3206-3216, 2018 03 20.
Article em En | MEDLINE | ID: mdl-29562177
The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article