Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum Rechts der Isar, Technische Universität München, Germany ; Genetik der Hautcarcinogenese, Deutsches Krebsforschungszentrum, Germany.
Curr Genomics. 2012 Sep;13(6):426-32. doi: 10.2174/138920212802510475.
In radiotherapy the normal tissue reaction is often a limiting factor for radiation treatment. Still there is no screening method, which predicts normal tissue reaction on radiotherapy, especially in comparison to tumor tissue, and therefore allows tailoring of the radiation dose to each patient. Here, we present a case of severe radiation-related side effects. We applied classical cytogenetic techniques (Giemsa-banding and staining of centromeric regions), the comet assay as well as multicolor fluorescence in situ hybridization on peripheral blood lymphocytes of this patient in order to determine the radio-sensitivity on the DNA level and to correlate these findings with the clinical outcome. Our investigations revealed abnormalities on chromosome 9, deficiencies in the DNA-repair capacity after radiation exposure and a high number of radiation induced chromosomal aberrations. A detected high amount of residual damage two or three hours after radiation exposure and repair as well as the high number of chromosomal aberrations (ChAs) suggests a correlation between repair capacity and radiation induced ChAs. We concluded that the detected abnormalities might serve as a genetic basis for the radio-sensitive phenotype of this patient. Taken together this report strengthens the idea that intensive DNA genomic analysis of individual patients can serve as the basis for more favourable treatment of cancer patients.
在放射治疗中,正常组织反应通常是放射治疗的限制因素。目前还没有筛选方法可以预测正常组织对放射治疗的反应,特别是与肿瘤组织相比,因此无法为每个患者量身定制放射剂量。在这里,我们报告了一例严重的放射相关副作用病例。我们应用经典细胞遗传学技术(吉姆萨带染色和着丝粒区染色)、彗星试验以及多色荧光原位杂交技术,对该患者的外周血淋巴细胞进行检测,以确定 DNA 水平的放射敏感性,并将这些发现与临床结果相关联。我们的研究发现,患者 9 号染色体异常、辐射暴露后 DNA 修复能力缺陷以及大量辐射诱导的染色体畸变。在辐射暴露后两到三个小时检测到大量残留损伤和修复,以及大量染色体畸变(ChAs),提示修复能力和辐射诱导的 ChAs 之间存在相关性。我们得出结论,检测到的异常可能是该患者放射敏感表型的遗传基础。总的来说,本报告支持这样一种观点,即对个体患者进行密集的 DNA 基因组分析可以作为更有利的癌症患者治疗的基础。