, Volume 115, Issue 6, pp 459–467 | Cite as

The breakage–fusion–bridge (BFB) cycle as a mechanism for generating genetic heterogeneity in osteosarcoma

  • Shamini Selvarajah
  • Maisa Yoshimoto
  • Paul C. Park
  • Georges Maire
  • Jana Paderova
  • Jane Bayani
  • Gloria Lim
  • Khaldoun Al-Romaih
  • Jeremy A. SquireEmail author
  • Maria Zielenska
Research article


Osteosarcoma (OS) is characterized by chromosomal instability and high copy number gene amplification. The breakage–fusion–bridge (BFB) cycle is a well-established mechanism of genome instability in tumors and in vitro models used to study the origins of complex chromosomal rearrangements and cancer genome amplification. To determine whether the BFB cycle could be increasing the de novo rate of formation of cytogenetic aberrations in OS, the frequency of anaphase bridge configurations and dicentric chromosomes in four OS cell lines was quantified. An increased level of anaphase bridges and dicentrics was observed in all the OS cell lines. There was also a strong association between the frequencies of anaphase bridges, dicentrics, centrosomal anomalies, and multipolar mitotic figures in all the OS cell lines, indicating a possible link in the mechanisms that led to the structural and numerical instabilities observed in OS. In summary, this study has provided strong support for the role of the BFB cycle in generating the extensive structural chromosome aberrations, as well as cell-to-cell cytogenetic variation observed in OS, thus conferring the genetic diversity for OS tumor progression.


Dicentric Chromosome Anaphase Bridge Inverted Duplication Atypical Lipomatous Tumor Multipolar Mitosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by funding from the National Cancer Institute of Canada and Canadian Institute of Health Research (Ph.D. fellowship to S.S.).


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Shamini Selvarajah
    • 1
    • 2
  • Maisa Yoshimoto
    • 3
  • Paul C. Park
    • 4
  • Georges Maire
    • 3
  • Jana Paderova
    • 3
  • Jane Bayani
    • 3
  • Gloria Lim
    • 1
  • Khaldoun Al-Romaih
    • 2
    • 3
  • Jeremy A. Squire
    • 2
    • 3
    • 5
    Email author
  • Maria Zielenska
    • 1
    • 2
  1. 1.Department of Pathology and Laboratory MedicineThe Hospital for Sick ChildrenTorontoCanada
  2. 2.Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  3. 3.Applied Molecular Oncology, Ontario Cancer InstitutePrincess Margaret HospitalTorontoCanada
  4. 4.Department of Pathology and Laboratory Medicine and PathobiologyOttawa General HospitalOttawaCanada
  5. 5.Department of Medical Biophysics, Faculty of MedicineUniversity of TorontoTorontoCanada

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