The Architecture and Evolution of Cancer Neochromosomes
Dale W Garsed, Owen J Marshall, Vincent DA Corbin, Arthur Hsu, Leon Di Stefano, Jan Schroeder, Jason Li, Zhi-Ping Feng, Bo W Kim, Mark Kowarsky, Ben Lansdell, Ross Brookwell, Ola Myklebost, Leonardo Meza-Zepeda, Andrew J Holloway, Florence Pedeutour, KH Andy Choo, Michael A Damore, Andrew J Deans, Anthony T Papenfuss Show all
CANCER CELL | CELL PRESS | Published : 2014
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 c..View full abstract
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Awarded by National Health and Medical Research Council (NHMRC)
Awarded by NHMRC
We thank Dr. Matt Burton, Dr. Meaghan Wall, Aurelie Copin, and Sophie Popkiss for their technical assistance. D.M.T. and A.T.P. were supported by a National Health and Medical Research Council (NHMRC) Project Grant (1004022) and the Liddy Shriver Sarcoma Initiative. D.M.T. was supported by an NHMRC Senior Research Fellowship (1003929). A.T.P. was supported by an NHMRC Career Development Fellowship (1003856) and an NHMRC Program Grant (1054618). The work benefitted from support by the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme. M.A.D. is an employee of AMGEN, Inc.