breakage-fusion-bridge
Definition: The breakage-fusion-bridge (BFB) cycle is a mechanism of genome instability in tumours and in in vitro models, used to study the origins of complex chromosomal rearrangements and cancer genome amplification. Advanced molecular cytogenetic techniques permit to investigate the contribution of the BFB cycle to the process of gene amplification and karyotypic complexity in tumors.
Examples
BFB-intermediates occur at a statistically significant frequency in osteosarcoma cell lines. Array CGH (aCGH) show complex amplicon structures consisting of microdeletions flanking focal amplifications in osteosarcoma-derived cell lines as well as osteosarcoma tumors. Data are consistent with the resolution of BFB anaphase bridges by DNA breaks, and concomitant loss of genomic material at or near the point of chromosome breakage.
head and neck squamous cell carcinomas (HNSCC)
About 45% of head and neck squamous cell carcinomas (HNSCC) are characterized by 11q13 amplification . This amplification occurs by a breakage-fusion-bridge (BFB) cycle mechanism.
The first step in the BFB cycle involves breakage and loss of distal 11q, from FRA11F (11q14.2) to 11qter. Consequently, numerous genes, including three critical genes involved in the DNA damage response pathway, MRE11A, ATM, and H2AFX are lost in the step preceding 11q13 amplification.
References
Parikh RA, White JS, Huang X, Schoppy DW, Baysal BE, Baskaran R, Bakkenist CJ, Saunders WS, Hsu LC, Romkes M, Gollin SM. Loss of distal 11q is associated with DNA repair deficiency and reduced sensitivity to ionizing radiation in head and neck squamous cell carcinoma. Genes Chromosomes Cancer. 2007 May 10;46(8):761-775. PMID: 17492757