Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm

Trends Mol Med. 2005 Dec;11(12):537-45. doi: 10.1016/j.molmed.2005.10.005. Epub 2005 Nov 14.

Abstract

Medulloblastomas often activate Hedgehog signaling inappropriately. The finding that mutations in components of this pathway are present only in few tumors suggests that additional genetic or epigenetic lesions can also lead to Hedgehog dysregulation. Chromosome 17p deletion, the most frequently detected genetic lesion in medulloblastoma, has recently been identified as a cause of unrestrained Hedgehog signaling. Such a deletion leads to the loss of REN(KCTD11), a novel Hedgehog antagonist, thus removing a checkpoint of Hedgehog-dependent events during cerebellum development and tumorigenesis. The disruption of additional Hedgehog modulators that map to 17p suggests a rationale for a multitargeted therapeutic strategy aimed at interrupting the cooperative activation of the Hedgehog pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cell Cycle Proteins
  • Chromosomes, Human, Pair 17 / genetics*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic / genetics
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic*
  • Hedgehog Proteins
  • Humans
  • Kruppel-Like Transcription Factors
  • Medulloblastoma / genetics*
  • Models, Biological*
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction / genetics*
  • Trans-Activators / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transferases
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • HIC1 protein, human
  • Hedgehog Proteins
  • Kruppel-Like Transcription Factors
  • MNT protein, human
  • Potassium Channels
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • KCTD11 protein, human
  • Transferases