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Cancer Cell. 2014 Nov 10;26(5):653-67. doi: 10.1016/j.ccell.2014.09.010. Epub 2014 Nov 10.

The architecture and evolution of cancer neochromosomes.

Author information

1
Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC 3010, Australia; Department of Pathology, University of Melbourne, VIC 3010, Australia.
2
Chromosome Research, Murdoch Childrens Research Institute, and Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, VIC 3052, Australia.
3
Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, VIC 3010, Australia; Bioinformatics and Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC, 3002, Australia.
4
Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
5
Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, VIC 3010, Australia.
6
Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
7
Sullivan Nicolaides Pathology, Indooroopilly, QLD 4068, Australia.
8
Department of Tumor Biology, Oslo University Hospital, Norwegian Radium Hospital, Oslo 0424, Norway.
9
Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice 06107, France.
10
Amgen, Thousand Oaks, CA 91320, USA.
11
St Vincent's Institute, Fitzroy, VIC 3065, Australia.
12
Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, VIC 3010, Australia; Department of Mathematics and Statistics, University of Melbourne, VIC, 3010, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC 3010, Australia; Bioinformatics and Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC, 3002, Australia. Electronic address: papenfuss@wehi.edu.au.
13
Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, VIC 3010, Australia; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia. Electronic address: d.thomas@garvan.org.au.

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.

PMID:
25517748
DOI:
10.1016/j.ccell.2014.09.010
[Indexed for MEDLINE]
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