Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma
Summary: 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 medulloblas...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718302997 |
| _version_ | 1819117471235309568 |
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| author | Walderik W. Zomerman Sabine L.A. Plasschaert Siobhan Conroy Frank J. Scherpen Tiny G.J. Meeuwsen-de Boer Harm J. Lourens Sergi Guerrero Llobet Marlinde J. Smit Lorian Slagter-Menkema Annika Seitz Corrie E.M. Gidding Esther Hulleman Pieter Wesseling Lisethe Meijer Leon C. van Kempen Anke van den Berg Daniël O. Warmerdam Frank A.E. Kruyt Floris Foijer Marcel A.T.M. van Vugt Wilfred F.A. den Dunnen Eelco W. Hoving Victor Guryev Eveline S.J.M. de Bont Sophia W.M. Bruggeman |
| author_facet | Walderik W. Zomerman Sabine L.A. Plasschaert Siobhan Conroy Frank J. Scherpen Tiny G.J. Meeuwsen-de Boer Harm J. Lourens Sergi Guerrero Llobet Marlinde J. Smit Lorian Slagter-Menkema Annika Seitz Corrie E.M. Gidding Esther Hulleman Pieter Wesseling Lisethe Meijer Leon C. van Kempen Anke van den Berg Daniël O. Warmerdam Frank A.E. Kruyt Floris Foijer Marcel A.T.M. van Vugt Wilfred F.A. den Dunnen Eelco W. Hoving Victor Guryev Eveline S.J.M. de Bont Sophia W.M. Bruggeman |
| author_sort | Walderik W. Zomerman |
| collection | DOAJ |
| description | Summary: 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. : Using peptide phosphorylation profiling, Zomerman et al. identify two medulloblastoma phosphoprotein-signaling profiles that have prognostic value and are potentially targetable. They find that these profiles extend across transcriptome-based subgroup borders. This suggests that diverse genetic information converges on common protein-signaling pathways and highlights protein-signaling as a unique information layer. Keywords: medulloblastoma, protein-signaling, protein synthesis, MYC, TP53, proteome, phosphoproteome |
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| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-22T05:33:30Z |
| publishDate | 2018-03-01 |
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| series | Cell Reports |
| spelling | doaj.art-29d5a08e9ade4e27a193d738913783712022-12-21T18:37:24ZengElsevierCell Reports2211-12472018-03-01221232063216Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human MedulloblastomaWalderik W. Zomerman0Sabine L.A. Plasschaert1Siobhan Conroy2Frank J. Scherpen3Tiny G.J. Meeuwsen-de Boer4Harm J. Lourens5Sergi Guerrero Llobet6Marlinde J. Smit7Lorian Slagter-Menkema8Annika Seitz9Corrie E.M. Gidding10Esther Hulleman11Pieter Wesseling12Lisethe Meijer13Leon C. van Kempen14Anke van den Berg15Daniël O. Warmerdam16Frank A.E. Kruyt17Floris Foijer18Marcel A.T.M. van Vugt19Wilfred F.A. den Dunnen20Eelco W. Hoving21Victor Guryev22Eveline S.J.M. de Bont23Sophia W.M. Bruggeman24Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartments 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 NetherlandsDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartment of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartment 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 Groningen, the NetherlandsDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartment of Pediatric Oncology/Pediatrics, Radboud University Medical Center Nijmegen, Geert Groteplein Zuid 10, 6525 HB Nijmegen, the NetherlandsDepartment of Pediatric Oncology/Hematology, Neuro-oncology Research Group, Cancer Center Amsterdam, VU University Medical Center Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, the NetherlandsPrincess 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 NetherlandsBeatrix Children’s Hospital, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartment 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, CanadaDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsiPSC CRISPR Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartment of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsiPSC 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 NetherlandsDepartment of Medical Oncology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartment 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 NetherlandsERIBA, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the NetherlandsDepartments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; Corresponding authorSummary: 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. : Using peptide phosphorylation profiling, Zomerman et al. identify two medulloblastoma phosphoprotein-signaling profiles that have prognostic value and are potentially targetable. They find that these profiles extend across transcriptome-based subgroup borders. This suggests that diverse genetic information converges on common protein-signaling pathways and highlights protein-signaling as a unique information layer. Keywords: medulloblastoma, protein-signaling, protein synthesis, MYC, TP53, proteome, phosphoproteomehttp://www.sciencedirect.com/science/article/pii/S2211124718302997 |
| spellingShingle | Walderik W. Zomerman Sabine L.A. Plasschaert Siobhan Conroy Frank J. Scherpen Tiny G.J. Meeuwsen-de Boer Harm J. Lourens Sergi Guerrero Llobet Marlinde J. Smit Lorian Slagter-Menkema Annika Seitz Corrie E.M. Gidding Esther Hulleman Pieter Wesseling Lisethe Meijer Leon C. van Kempen Anke van den Berg Daniël O. Warmerdam Frank A.E. Kruyt Floris Foijer Marcel A.T.M. van Vugt Wilfred F.A. den Dunnen Eelco W. Hoving Victor Guryev Eveline S.J.M. de Bont Sophia W.M. Bruggeman Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma Cell Reports |
| title | Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma |
| title_full | Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma |
| title_fullStr | Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma |
| title_full_unstemmed | Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma |
| title_short | Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma |
| title_sort | identification of two protein signaling states delineating transcriptionally heterogeneous human medulloblastoma |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718302997 |
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