title: Hedgehog checkpoints in medulloblastoma: the chromosome 17p deletion paradigm.
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.
authors.affiliation: Department of Experimental Medicine and Pathology, La Sapienza University, Viale Regina Elena 324, 00161 Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
authors.forename: Enrico
authors.initials: E
authors.lastname: De Smaele
authors.forename: Lucia
authors.initials: L
authors.lastname: Di Marcotullio
authors.forename: Isabella
authors.initials: I
authors.lastname: Screpanti
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
mesh_terms: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008527:Medulloblastoma / Q000235:genetics*; D008954:Models, Biological; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014166:Transferases; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C499808:HIC1 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C106465:MNT protein, human; D015221:Potassium Channels; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C488725:KCTD11 protein, human; D014166:Transferases