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Telomere dysfunction and chromothripsis
Author(s) -
Ernst Aurélie,
Jones David T.W.,
Maass Kendra K.,
Rode Agata,
Deeg Katharina I.,
Jebaraj Billy Michael Chelliah,
Korshunov Andrey,
Hovestadt Volker,
Tainsky Michael A.,
Pajtler Kristian W.,
Bender Sebastian,
Brabetz Sebastian,
Gröbner Susanne,
Kool Marcel,
Devens Frauke,
Edelmann Jennifer,
Zhang Cindy,
CasteloBranco Pedro,
Tabori Uri,
Malkin David,
Rippe Karsten,
Stilgenbauer Stephan,
Pfister Stefan M.,
Zapatka Marc,
Lichter Peter
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30033
Subject(s) - chromothripsis , telomere , genome instability , biology , chromosome instability , genome , clone (java method) , genetics , cancer research , chromosome , dna , gene , dna damage
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.