title: Telomere dysfunction and chromothripsis.
abstract: Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome.
authors: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Aurélie
authors: A
authors: Ernst
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: David T W
authors: DT
authors: Jones
authors: Division Functional Architecture of the Cell, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Kendra K
authors: KK
authors: Maass
authors: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Agata
authors: A
authors: Rode
authors: Genome Organization and Function, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Katharina I
authors: KI
authors: Deeg
authors: Department of Internal Medicine III, University of Ulm, Germany.
authors: Billy Michael Chelliah
authors: BM
authors: Jebaraj
authors: Department of Neuropathology University Hospital, Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Andrey
authors: A
authors: Korshunov
authors: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Volker
authors: V
authors: Hovestadt
authors: Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI.
authors: Michael A
authors: MA
authors: Tainsky
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Kristian W
authors: KW
authors: Pajtler
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Sebastian
authors: S
authors: Bender
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Sebastian
authors: S
authors: Brabetz
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Susanne
authors: S
authors: Gröbner
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Marcel
authors: M
authors: Kool
authors: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Frauke
authors: F
authors: Devens
authors: Department of Internal Medicine III, University of Ulm, Germany.
authors: Jennifer
authors: J
authors: Edelmann
authors: Division of Pediatric Hematology-Oncology and the Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
authors: Cindy
authors: C
authors: Zhang
authors: Division of Pediatric Hematology-Oncology and the Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
authors: Pedro
authors: P
authors: Castelo-Branco
authors: Division of Pediatric Hematology-Oncology and the Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
authors: Uri
authors: U
authors: Tabori
authors: Division of Hematology/Oncology and Department of Pediatrics, The Hospital for Sick Children and Department of Pediatrics, University of Toronto, Toronto, ON, Canada.
authors: David
authors: D
authors: Malkin
authors: Genome Organization and Function, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Karsten
authors: K
authors: Rippe
authors: Department of Internal Medicine III, University of Ulm, Germany.
authors: Stephan
authors: S
authors: Stilgenbauer
authors: Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Stefan M
authors: SM
authors: Pfister
authors: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Marc
authors: M
authors: Zapatka
authors: Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors: Peter
authors: P
authors: Lichter
mesh_terms: D016022:Case-Control Studies; D002528:Cerebellar Neoplasms / Q000201:enzymology / Q000235:genetics*; D025063:Chromosome Disorders / Q000201:enzymology / Q000235:genetics; D004806:Ependymoma / Q000201:enzymology / Q000235:genetics; D015870:Gene Expression; D042822:Genomic Instability; D006801:Humans; D008527:Medulloblastoma / Q000201:enzymology / Q000235:genetics*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis
chemical_list: C509186:TERT protein, human; D019098:Telomerase
keywords: chromothripsis; genome instability; genomic catastrophe; telomere