Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma

Cell Rep. 2018 Mar 20;22(12):3206-3216. doi: 10.1016/j.celrep.2018.02.089.


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.

Keywords: MYC; TP53; medulloblastoma; phosphoproteome; protein synthesis; protein-signaling; proteome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cerebellar Neoplasms / genetics
  • Cerebellar Neoplasms / metabolism*
  • Cerebellar Neoplasms / pathology
  • Gene Expression Profiling
  • Hedgehog Proteins / metabolism*
  • Humans
  • Medulloblastoma / genetics
  • Medulloblastoma / metabolism*
  • Medulloblastoma / pathology
  • Phosphorylation
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Tumor Suppressor Protein p53 / genetics


  • Hedgehog Proteins
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • TP53 protein, human
  • Tumor Suppressor Protein p53