title: New aspects on chromosomal instability: chromosomal break-points in Fanconi anemia patients co-localize on the molecular level with fragile sites.
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 evolutionary-conserved chromosomal break-points. The also suggested co-localization 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.
authors.affiliation: Jena University Hospital, Institute of Human Genetics and Anthropology, D-07743 Jena, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Schoder
authors.forename: Thomas
authors.initials: T
authors.lastname: Liehr
authors.forename: Eunike
authors.initials: E
authors.lastname: Velleuer
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wilhelm
authors.forename: Nancy
authors.initials: N
authors.lastname: Blaurock
authors.forename: Anja
authors.initials: A
authors.lastname: Weise
authors.forename: Kristin
authors.initials: K
authors.lastname: Mrasek
mesh_terms: D000293:Adolescent; D043171:Chromosomal Instability / Q000235:genetics*; D043283:Chromosome Fragile Sites / Q000235:genetics*; D005199:Fanconi Anemia / Q000235:genetics*; D005260:Female; D006801:Humans; D007621:Karyotyping