The architecture and evolution of cancer neochromosomes
Details
Publication Year 2014-11-10, Volume 26, Issue #5, Page 653-667
Journal Title
Cancer Cell
Publication Type
Journal Article
Abstract
We isolated and analyzed, at single-nucleotide resolution, cancer-associated neochromosomes from well- and/or dedifferentiated liposarcomas. Neochromosomes, which can exceed 600 Mb in size, initially arise as circular structures following chromothripsis involving chromosome 12. The core of the neochromosome is amplified, rearranged, and corroded through hundreds of breakage-fusion-bridge cycles. Under selective pressure, amplified oncogenes are overexpressed, while coamplified passenger genes may be silenced epigenetically. New material may be captured during punctuated chromothriptic events. Centromeric corrosion leads to crisis, which is resolved through neocentromere formation or native centromere capture. Finally, amplification terminates, and the neochromosome core is stabilized in linear form by telomere capture. This study investigates the dynamic mutational processes underlying the life history of a special form of cancer mutation.
Publisher
Cell Press
WEHI Research Division(s)
Bioinformatics
NHMRC Grants
NHMRC/1003856 NHMRC/1054618
Rights Notice
Copyright © 2014 Elsevier Inc. All rights reserved.


Creation Date: 2014-12-19 11:44:53
Last Modified: 2016-02-09 05:28:21
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