Institute of Genetics and Cytolog, National Academy of Sciences of Belarus, Minsk, Republic of Belarus.
Biomarkers. 2012 May;17(3):201-8. doi: 10.3109/1354750X.2011.651157. Epub 2012 Mar 21.
The study of genome integrity in some genetic disorders has diagnostic and prognostic importance because of the evident relationship between genome instability and both DNA repair deficiencies and cancer predisposition.
The objective was to compare the chromosomal and DNA damage responses in lymphocytes from patients with Nijmegen breakage syndrome (NBS), Fanconi anemia (FA) and Williams-Beuren syndrome (WBS) to find additional biomarkers of genome instability.
The cytogenetic approaches were combined with the alkaline Comet assay to estimate genome integrity in cultured or freshly isolated and H(2)O(2)-treated lymphocytes.
Basal frequencies of chromosome aberrations were significantly increased in NBS/FA probands and NBS heterozygous carriers. The NBS diagnosis was confirmed by detecting site-specific rearrangements, while the mitomycin C (MMC)-stress test was highly positive in a FA patient. Among patients with suspected WBS, 12 individuals had a 7q11.23 microdeletion. In the Comet assay, genome instability was revealed in all three disorders, impaired capacity to repair oxidative damage being observed in NBS and WBS in contrast to FA and controls.
The results indicate that the estimates of DNA damage response may be proposed as efficient biomarkers for detecting and characterizing genome instability in the genetic disorders under study.
由于基因组不稳定性与 DNA 修复缺陷和癌症易感性之间存在明显的关系，因此研究某些遗传疾病中的基因组完整性具有诊断和预后意义。
旨在比较尼曼匹克氏症（NBS）、范可尼贫血症（FA）和威廉姆斯综合征（WBS）患者淋巴细胞中的染色体和 DNA 损伤反应，以寻找额外的基因组不稳定性生物标志物。
将细胞遗传学方法与碱性彗星试验相结合，以评估培养或新鲜分离并经 H2O2 处理的淋巴细胞中的基因组完整性。
NBS/FA 先证者和 NBS 杂合子携带者的染色体畸变基础频率显著增加。通过检测特异性重排来确认 NBS 诊断，而 FA 患者的丝裂霉素 C（MMC）应激试验呈高度阳性。在疑似 WBS 的患者中，有 12 人存在 7q11.23 微缺失。在彗星试验中，所有三种疾病均显示出基因组不稳定性，与 FA 和对照组相比，NBS 和 WBS 中观察到氧化损伤修复能力受损。
结果表明，DNA 损伤反应的评估可以作为检测和表征所研究遗传疾病中基因组不稳定性的有效生物标志物。
