The breakage-fusion-bridge (BFB) cycle as a mechanism for generating genetic heterogeneity in osteosarcoma.
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.
Selvarajah
Shamini
S
Department of Pathology and Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Yoshimoto
Maisa
M
Park
Paul C
PC
Maire
Georges
G
Paderova
Jana
J
Bayani
Jane
J
Lim
Gloria
G
Al-Romaih
Khaldoun
K
Squire
Jeremy A
JA
Zielenska
Maria
M
D000705:Anaphase; D001324:Autoantigens / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D000076247:Centromere Protein A; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019457:Chromosome Breakage; D020223:Chromosome Painting; D002877:Chromosomes, Human; D050939:Gene Fusion; D018740:Genetic Heterogeneity; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
D001324:Autoantigens; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone