美国国家癌症研究所Lindsay M. Morton 和Stephen J. Chanock小组的最新研究揭示了切尔诺贝利事故后与辐射相关甲状腺乳头状癌（PTC）的基因组图谱。2021年4月22日出版的《科学》发表了这项成果。
研究人员分析了乌克兰440个PTC患者的基因组、转录组和表观基因组特征（包括359个暴露于辐射的儿童和81个1986年以后出生未受辐射的儿童）。PTC显示出辐射剂量依赖性融合驱动因子富集，这些因子几乎集中在有丝分裂原激活蛋白激酶途径中，并且增加了小片段缺失和结构变异，这些变异是非同源末端连接修复的克隆特征。
与辐射有关的基因组改变对于那些年幼接触者更为明显。转录组学和表观基因组学特征与诱变事件密切相关，但与辐射剂量无关。该研究结果表明，DNA双链断裂是早期致癌事件，可在暴露于环境辐射后促进PTC的发生。
附：英文原文
Title: Radiation-related genomic profile of papillary thyroid cancer after the Chernobyl accident
Author: Lindsay M. Morton, Danielle M. Karyadi, Chip Stewart, Tetiana I. Bogdanova, Eric T. Dawson, Mia K. Steinberg, Jieqiong Dai, Stephen W. Hartley, Sara J. Schonfeld, Joshua N. Sampson, Yosi Maruvka, Vidushi Kapoor, Dale A. Ramsden, Juan Carvajal-Garcia, Charles M. Perou, Joel S. Parker, Marko Krznaric, Meredith Yeager, Joseph F. Boland, Amy Hutchinson, Belynda D. Hicks, Casey L. Dagnall, Julie M. Gastier-Foster, Jay Bowen, Olivia Lee, Mitchell J. Machiela, Elizabeth K. Cahoon, Alina V. Brenner, Kiyohiko Mabuchi, Vladimir Drozdovitch, Sergii Masiuk, Mykola Chepurny, Liudmyla Yu. Zurnadzhy, Maureen Hatch, Amy Berrington de Gonzalez, Gerry A. Thomas, Mykola D. Tronko, Gad Getz, Stephen J. Chanock
Issue&Volume: 2021/04/22
Abstract: The 1986 Chernobyl nuclear power plant accident increased papillary thyroid cancer (PTC) incidence in surrounding regions, particularly for 131I-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (359 with estimated childhood 131I 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 non-homologous end-joining repair. Radiation-related genomic alterations were more pronounced for those 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 following environmental radiation exposure.
DOI: 10.1126/science.abg2538
Source: https://science.sciencemag.org/content/early/2021/04/21/science.abg2538