Clinical, Molecular- and Cytogenetic Analysis of a Case of Severe Radio- Sensitivity

Abstract

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.

Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers: A Review

“…It should be noted that, from the beginning, cytogenetic analyses were highly informative for confirming the radiosensitivity post factum in individual cases as identified by clinical symptoms. As a rule, patients with abnormal tissue radiosensitivity displayed a higher outcome of ChA per unit dose induced in lymphocytes by ex vivo irradiation [ 59 , 60 , 61 , 62 ]. Thus, radiation biomarkers can be used effectively for revealing a possible mechanism of radiosensitivity, particularly a malfunction of the DNA repair machinery involved in the ChA formation.…”

“…Importantly, elevated rates of ChA induced in vitro have been observed in clinically radiosensitive patients who did not have any constitutional chromosomal abnormalities [ 59 ], known genetic disorders with increased radiosensitivity [ 60 , 62 ], or apparent hereditary chromosome instability, cancer prone syndromes [ 61 ]. The relationship between the two latter categories is not simple.…”

Combined pretreatment with 18F-FDG PET/CT and Comet assay guides the concurrent chemoradiotherapy of locally advanced cervical cancer: study protocol for a randomized controlled trial

“…The Comet assay, also known as single-cell gel electrophoresis analysis, can evaluate the sensitivity of the tumor to radiotherapy, the proportion of active and hypoxic tumor cells, and the heterogeneity of the tumor response to treatment [ 9 , 19 – 22 ]. Preclinical studies have shown that the Comet assay is consistent with the classic clone formation assay, which is a potential method for the clinical detection and analysis of radiation sensitivity [ 20 , 23 ]. Using the Comet assay, higher doses of irradiation can be delivered to the tumor or a tumor region with low sensitivity to achieve individualized radiotherapy.…”