| Literature DB >> 29562177 |
Walderik W Zomerman1, Sabine L A Plasschaert2, Siobhan Conroy3, Frank J Scherpen1, Tiny G J Meeuwsen-de Boer1, Harm J Lourens1, Sergi Guerrero Llobet4, Marlinde J Smit1, Lorian Slagter-Menkema5, Annika Seitz3, Corrie E M Gidding6, Esther Hulleman7, Pieter Wesseling8, Lisethe Meijer9, Leon C van Kempen10, Anke van den Berg3, Daniël O Warmerdam11, Frank A E Kruyt4, Floris Foijer12, Marcel A T M van Vugt4, Wilfred F A den Dunnen3, Eelco W Hoving13, Victor Guryev14, Eveline S J M de Bont1, Sophia W M Bruggeman15.
Abstract
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.Entities:
Keywords: MYC; TP53; medulloblastoma; phosphoproteome; protein synthesis; protein-signaling; proteome
Mesh：
Substances：
Year: 2018 PMID： 29562177 DOI： 10.1016/j.celrep.2018.02.089
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423