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Int J Cancer. 2016 Jun 15;138(12):2905-14. doi: 10.1002/ijc.30033. Epub 2016 Feb 29.

Telomere dysfunction and chromothripsis.

Author information

1
Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
Division Functional Architecture of the Cell, German Cancer Research Center (DKFZ), Heidelberg, Germany.
4
Genome Organization and Function, German Cancer Research Center (DKFZ), Heidelberg, Germany.
5
Department of Internal Medicine III, University of Ulm, Germany.
6
Department of Neuropathology University Hospital, Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
7
Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI.
8
Division of Pediatric Hematology-Oncology and the Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
9
Division of Hematology/Oncology and Department of Pediatrics, The Hospital for Sick Children and Department of Pediatrics, University of Toronto, Toronto, ON, Canada.

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.

KEYWORDS:

chromothripsis; genome instability; genomic catastrophe; telomere

PMID:
26856307
DOI:
10.1002/ijc.30033
[Indexed for MEDLINE]
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