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Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident
Science ( IF 44.7 ) Pub Date : 2021-05-14 , DOI: 10.1126/science.abg2538
Lindsay M Morton 1 , Danielle M Karyadi 2 , Chip Stewart 3 , Tetiana I Bogdanova 4 , Eric T Dawson 2, 5 , Mia K Steinberg 6 , Jieqiong Dai 6 , Stephen W Hartley 2 , Sara J Schonfeld 1 , Joshua N Sampson 7 , Yosef E Maruvka 3 , Vidushi Kapoor 6 , Dale A Ramsden 8 , Juan Carvajal-Garcia 9 , Charles M Perou 10, 11 , Joel S Parker 11 , Marko Krznaric 12 , Meredith Yeager 6 , Joseph F Boland 6 , Amy Hutchinson 6 , Belynda D Hicks 6 , Casey L Dagnall 6 , Julie M Gastier-Foster 13, 14 , Jay Bowen 13 , Olivia Lee 2 , Mitchell J Machiela 15 , Elizabeth K Cahoon 1 , Alina V Brenner 16 , Kiyohiko Mabuchi 1 , Vladimir Drozdovitch 1 , Sergii Masiuk 17 , Mykola Chepurny 17 , Liudmyla Yu Zurnadzhy 4 , Maureen Hatch 1 , Amy Berrington de Gonzalez 1 , Gerry A Thomas 12 , Mykola D Tronko 18 , Gad Getz 3, 19, 20 , Stephen J Chanock 2
Affiliation  

The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (131I)–exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals 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 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.



中文翻译:

切尔诺贝利事故后甲状腺乳头状癌的辐射相关基因组图谱

1986 年切尔诺贝利核电站事故增加了周边地区甲状腺乳头状癌 (PTC) 的发病率,特别是接触放射性碘 ( 131 I) 的儿童。我们分析了来自乌克兰的 440 名 PTC 的基因组、转录组和表观基因组特征(来自 359 名估计童年期为131 岁的个体)I 暴露和 81 名 1986 年后出生的未暴露儿童)。PTC表现出融合驱动因素的辐射剂量依赖性富集,几乎全部在丝裂原激活蛋白激酶途径中,并且小缺失和简单/平衡结构变异的增加,这些变异是克隆性的,具有非同源末端连接修复的特征。对于暴露时年龄较小的个体来说,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使 PTC 生长。

更新日期:2021-05-14
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