The Architecture and Evolution of Cancer Neochromosomes

Dale W. Garsed, Owen J. Marshall, Vincent D.A. Corbin, Arthur Hsu, Leon DiStefano, Jan Schröder, Jason Li, Zhi Ping Feng, Bo W. Kim, Mark Kowarsky, Ben Lansdell, Ross Brookwell, Ola Myklebost, Leonardo Meza-Zepeda, Andrew J. Holloway, Florence Pedeutour, K. H.Andy Choo, Michael A. Damore, Andrew J. Deans, Anthony T. PapenfussDavid M. Thomas

Research output: Contribution to journalArticleResearchpeer-review

82 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)653-667
Number of pages15
JournalCancer Cell
Volume26
Issue number5
DOIs
Publication statusPublished - 10 Nov 2014
Externally publishedYes

Cite this