New aspects on chromosomal instability: Chromosomal break-points in Fanconi anemia patients co-localize on the molecular level with fragile sites

Abstract

Abstract. Within cytogenetic preparations chromosomal breaks can be observed in patients suffering from Fanconi anemia (FA), a recessively inherited syndrome with an extremely elevated cancer risk, but also in healthy individuals as so-called fragile sites (FS). It is known that FS cytogenetically co-localize with tumor-and evolutionaryconserved chromosomal break-points. The also suggested colocalization of FS and FA associated break-points (FA-bp) was studied here for the first time systematically by molecular cytogenetics. Metaphase chromosomes were obtained from lymphocytes of two FA patients (FANC-A and FANC-C, respectively). Overall 50.58% of the investigated FA-bp correspond to cytogenetic regions with known FS. A detailed molecular cytogenetic study applying FS-spanning probes revealed that 24/29 (82.8%) of analyzed FS are in concordance with FA-bp. Notably, FA-bp show a distribution pattern deviating from that of Aphidicolin induced FS. FA-bp appear more frequently within GTG-light bands and additionally, a yet unreported correlation was observed between break rate and chromosomal banding level. In future, FA-bp might serve as model for the mapping and analysis of otherwise rarely observable FS.