Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis
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Gascoigne_2013-Induced dicentric chromosome.pdf
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Author(s)
Gascoigne, Karen E.
Cheeseman, Iain M
Date Issued
June 2013
Journal
Chromosome Research
Publisher
Springer-Verlag
Citation
Gascoigne, Karen E., and Iain M. Cheeseman. “Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis.” Chromosome Research 21, no. 4 (July 22, 2013): 407-418.
Version
Final published version
Abstract
Chromosomal rearrangements can radically alter gene products and their function, driving tumor formation or progression. However, the molecular origins and evolution of such rearrangements are varied and poorly understood, with cancer cells often containing multiple, complex rearrangements. One mechanism that can lead to genomic rearrangements is the formation of a “dicentric” chromosome containing two functional centromeres. Indeed, such dicentric chromosomes have been observed in cancer cells. Here, we tested the ability of a single dicentric chromosome to contribute to genomic instability and neoplastic conversion in vertebrate cells. We developed a system to transiently and reversibly induce dicentric chromosome formation on a single chromosome with high temporal control. We find that induced dicentric chromosomes are frequently damaged and mis-segregated during mitosis, and that this leads to extensive chromosomal rearrangements including translocations with other chromosomes. Populations of pre-neoplastic cells in which a single dicentric chromosome is induced acquire extensive genomic instability and display hallmarks of cellular transformation including anchorage-independent growth in soft agar. Our results suggest that a single dicentric chromosome could contribute to tumor initiation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1007/s10577-013-9368-6
