title: Pathways to chromothripsis.
abstract: Chromothripsis is a recently recognized mode of genetic instability that generates chromosomes with strikingly large numbers of segmental re-arrangements. While the characterization of these derivative chromosomes has provided new insights into the processes by which cancer genomes can evolve, the underlying signaling events and molecular mechanisms remain unknown. In medulloblastomas, chromothripsis has been observed to occur in the context of mutational inactivation of p53 and activation of the canonical Hedgehog (Hh) pathway. Recent studies have illuminated mechanistic links between these 2 signaling pathways, including a novel PTCH1 homolog that is regulated by p53. Here, we integrate this new pathway into a hypothetical model for the catastrophic DNA breakage that appears to trigger profound chromosomal rearrangements.
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences ; The Kimmel Cancer Center at Johns Hopkins ; Baltimore MD USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ivkov
authors.affiliation: a Department of Radiation Oncology and Molecular Radiation Sciences ; The Kimmel Cancer Center at Johns Hopkins ; Baltimore MD USA.
authors.forename: Fred
authors.initials: F
authors.lastname: Bunz
mesh_terms: D043171:Chromosomal Instability; D053960:DNA Breaks; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D053823:Hedgehog Proteins; C000595194:PTCHD4 protein, human; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53
keywords: PTCH53; chromothripsis; hedgehog; medulloblastoma; p53