切尔诺贝利事故后甲状腺乳头状癌的辐射相关基因组特征。
Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.
机构信息
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Laboratory of Genetic Susceptibility, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
出版信息
Science. 2021 May 14;372(6543). doi: 10.1126/science.abg2538. Epub 2021 Apr 22.
The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Radiation-related genomic alterations were more pronounced for individuals who were younger at exposure. Transcriptomic and epigenomic features were strongly associated with driver events but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth after environmental radiation exposure.
1986 年切尔诺贝利核电厂事故增加了周边地区的甲状腺乳头癌（PTC）的发病率，尤其是对放射性碘（I）暴露的儿童。我们分析了来自乌克兰的 440 例 PTC 的基因组、转录组和表观基因组特征（来自 359 名据估计有儿童时期 I 暴露的个体和 81 名 1986 年后出生的未暴露儿童）。PTC 显示出辐射剂量依赖性融合驱动子的富集，几乎全部在丝裂原活化蛋白激酶途径中，并且小缺失和简单/平衡结构变体的增加呈克隆性，具有非同源末端连接修复的特征。在暴露时年龄较小的个体中，与辐射相关的基因组改变更为明显。转录组和表观基因组特征与驱动事件密切相关，但与辐射剂量无关。我们的研究结果表明，DNA 双链断裂是早期致癌事件，随后在环境辐射暴露后促进 PTC 的生长。
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