Jena University Hospital, Institute of Human Genetics and Anthropology, D-07743 Jena, Germany.
Int J Oncol. 2010 Feb;36(2):307-12.
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.
在患有范可尼贫血（FA）的患者的细胞遗传学制剂中可以观察到染色体断裂，FA 是一种隐性遗传综合征，癌症风险极高，但在健康个体中也可以观察到所谓的脆性部位（FS）。已知 FS 在细胞遗传学上与肿瘤和进化保守的染色体断裂点共定位。本研究首次通过分子细胞遗传学系统地研究了 FS 和 FA 相关断裂点（FA-bp）的共定位。从中分别获得了两名 FA 患者（FANC-A 和 FANC-C）的淋巴细胞中期染色体。总共调查的 FA-bp 中有 50.58%与已知 FS 的细胞遗传学区域相对应。应用 FS 跨越探针进行的详细分子细胞遗传学研究表明，分析的 FS 中有 24/29（82.8%）与 FA-bp 一致。值得注意的是，FA-bp 的分布模式与阿非迪可诱导的 FS 不同。FA-bp 更频繁地出现在 GTG 亮带内，此外，还观察到断裂率与染色体带水平之间存在未报道的相关性。将来，FA-bp 可能作为映射和分析其他罕见观察到的 FS 的模型。
