title: The architecture and evolution of cancer neochromosomes.
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.
authors.affiliation: 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.
authors.forename: Dale W
authors.initials: DW
authors.lastname: Garsed
authors.affiliation: Chromosome Research, Murdoch Childrens Research Institute, and Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Owen J
authors.initials: OJ
authors.lastname: Marshall
authors.affiliation: 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.
authors.forename: Vincent D A
authors.initials: VD
authors.lastname: Corbin
authors.affiliation: Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Arthur
authors.initials: A
authors.lastname: Hsu
authors.affiliation: Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Leon
authors.initials: L
authors.lastname: Di Stefano
authors.affiliation: Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, VIC 3010, Australia.
authors.forename: Jan
authors.initials: J
authors.lastname: Schröder
authors.affiliation: Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Li
authors.affiliation: Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, VIC 3010, Australia.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: Chromosome Research, Murdoch Childrens Research Institute, and Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: Bo W
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Kowarsky
authors.affiliation: Bioinformatics Division, The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Lansdell
authors.affiliation: Sullivan Nicolaides Pathology, Indooroopilly, QLD 4068, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Brookwell
authors.affiliation: Department of Tumor Biology, Oslo University Hospital, Norwegian Radium Hospital, Oslo 0424, Norway.
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
authors.affiliation: Department of Tumor Biology, Oslo University Hospital, Norwegian Radium Hospital, Oslo 0424, Norway.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Meza-Zepeda
authors.affiliation: Cancer Genomics, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Holloway
authors.affiliation: Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice 06107, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Pedeutour
authors.affiliation: Chromosome Research, Murdoch Childrens Research Institute, and Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, VIC 3052, Australia.
authors.forename: K H Andy
authors.initials: KH
authors.lastname: Choo
authors.affiliation: Amgen, Thousand Oaks, CA 91320, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Damore
authors.affiliation: St Vincent's Institute, Fitzroy, VIC 3065, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Deans
authors.affiliation: 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.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Papenfuss
authors.affiliation: 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.
authors.forename: David M
authors.initials: DM
authors.lastname: Thomas
mesh_terms: D000368:Aged; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D002503:Centromere / Q000235:genetics; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics*; D005260:Female; D006801:Humans; D008080:Liposarcoma / Q000235:genetics* / Q000473:pathology; D008957:Models, Genetic; D016296:Mutagenesis; D009857:Oncogenes; D012186:Retroperitoneal Neoplasms / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic