辐射诱导的葡萄膜黑色素瘤 DNA 损伤受剂量传递和 3 号染色体状态的影响。
Radiation-Induced DNA Damage in Uveal Melanoma Is Influenced by Dose Delivery and Chromosome 3 Status.
机构信息
Department of Ophthalmology, University Clinic Schleswig-Holstein (UKSH), University of Lübeck, Lübeck, Germany.
Department of Ophthalmology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
出版信息
Invest Ophthalmol Vis Sci. 2024 Jun 3;65(6):7. doi: 10.1167/iovs.65.6.7.
PURPOSE
The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status.
METHODS
A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization.
RESULTS
The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05).
CONCLUSIONS
Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.
目的
本研究旨在分析原发性葡萄膜黑色素瘤（UM）的 DNA 断裂程度与放疗剂量（单次剂量与分次剂量）和单体型 3 状态的关系。
方法
共纳入 54 例 UM 患者。23 例患者接受立体定向放疗（SRT），其中 8 例接受单次剂量 SRT（sdSRT）治疗，15 例接受分次剂量 SRT（fSRT）治疗。通过 TUNEL 检测法观察离体或经内切除肿瘤中的 DNA 断裂，并通过测量 TUNEL 阳性面积进行定量分析。采用免疫组织化学法分析蛋白表达。通过免疫荧光原位杂交法检测染色体 3 与蛋白的共检测。
结果
与未照射组织相比，总照射组的 DNA 断裂量增加了 2.7 倍（P < 0.001）。接受 fSRT 治疗的肿瘤受影响更为严重，与单次（高）剂量照射（sdSRT）后的病例相比，显示出 2.1 倍的更多 DNA 损伤（P = 0.007）。单体型 3 肿瘤的 DNA 断裂较二倍体 3 样本少（P = 0.004）。与 fSRT 和 sdSRT 联合组中无转移的癌症患者相比，放疗后发生转移的患者与单体型 3 存在相关性，且 DNA 断裂较少（P < 0.05）。
结论
与单次剂量治疗相比，原发性 UM 中的分次照射导致更多的 DNA 损伤。由于单体型 3 的肿瘤比二倍体 3 的肿瘤显示出更少的 DNA 断裂，这可能表明它们的放射敏感性较低，这可能会影响照射的疗效。
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