Format

Send to

Choose Destination
Cancer Cell. 2016 Jan 11;29(1):5-16. doi: 10.1016/j.ccell.2015.12.003.

The Interaction of Myc with Miz1 Defines Medulloblastoma Subgroup Identity.

Author information

1
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
2
Theodor Boveri Institute, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
3
German Cancer Research Center (DKFZ), Division of Pediatric Neurooncology (B062) Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
4
Department of Pathology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
5
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
6
Comprehensive Cancer Center Mainfranken, University of Würzburg, Josef-Schneider-Str.6, 97080 Würzburg, Germany.
7
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, 262 Danny Thomas Place, Memphis, TN 38105, USA.
#
Contributed equally

Abstract

Four distinct subgroups of cerebellar medulloblastomas (MBs) differ in their histopathology, molecular profiles, and prognosis. c-Myc (Myc) or MycN overexpression in granule neuron progenitors (GNPs) induces Group 3 (G3) or Sonic Hedgehog (SHH) MBs, respectively. Differences in Myc and MycN transcriptional profiles depend, in part, on their interaction with Miz1, which binds strongly to Myc but not MycN, to target sites on chromatin. Myc suppresses ciliogenesis and reprograms the transcriptome of SHH-dependent GNPs through Miz1-dependent gene repression to maintain stemness. Genetic disruption of the Myc/Miz1 interaction inhibited G3 MB development. Target genes of Myc/Miz1 are repressed in human G3 MBs but not in other subgroups. Therefore, the Myc/Miz1 interaction is a defining hallmark of G3 MB development.

Comment in

PMID:
26766587
PMCID:
PMC4714043
DOI:
10.1016/j.ccell.2015.12.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center