Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.
Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident.
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DOI：
10.1126/science.abg2538
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发表时间：
2021-05-14
期刊：
影响因子：
56.9
通讯作者：
Chanock, Stephen J.
中科院分区：
文献类型：
--
作者：
Morton, Lindsay M.;Karyadi, Danielle M.;Stewart, Chip;Bogdanova, Tetiana, I;Dawson, Eric T.;Steinberg, Mia K.;Dai, Jieqiong;Hartley, Stephen W.;Schonfeld, Sara J.;Sampson, Joshua N.;Maruvka, Yosef E.;Kapoor, Vidushi;Ramsden, Dale A.;Carvajal-Garcia, Juan;Perou, Charles M.;Parker, Joel S.;Krznaric, Marko;Yeager, Meredith;Boland, Joseph F.;Hutchinson, Amy;Hicks, Belynda D.;Dagnall, Casey L.;Gastier-Foster, Julie M.;Bowen, Jay;Lee, Olivia;Machiela, Mitchell J.;Cahoon, Elizabeth K.;Brenner, Alina, V;Mabuchi, Kiyohiko;Drozdovitch, Vladimir;Masiuk, Sergii;Chepurny, Mykola;Zurnadzhy, Liudmyla Yu;Hatch, Maureen;de Gonzalez, Amy Berrington;Thomas, Gerry A.;Tronko, Mykola D.;Getz, Gad;Chanock, Stephen J.
1986年切尔诺贝利核电站事故增加了周边地区乳头状甲状腺癌（PTC）的发病率，特别是对131 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（359例估计儿童期131 I暴露，81例1986年以后出生的未暴露儿童）。PTC显示出融合驱动因子的辐射剂量依赖性富集，几乎所有都在促分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是克隆的，并且具有非同源末端连接修复的标志。与辐射相关的基因组改变在那些年轻人中更为明显。转录组学和表观基因组学特征与驱动事件密切相关，但与辐射剂量无关。我们的研究结果指出，DNA双链断裂是早期致癌事件，随后使PTC生长环境辐射暴露后。切尔诺贝利事故后甲状腺乳头状癌表现出克隆DNA双链断裂的辐射剂量依赖性增加。
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. Post-Chernobyl papillary thyroid cancers demonstrate radiation dose-dependent increases in clonal DNA double-strand breaks.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
16.6
作者：
Behjati, Sam;Gundem, Gunes;Wedge, David C.;Roberts, Nicola D.;Tarpey, Patrick S.;Cooke, Susanna L.;Van Loo, Peter;Alexandrov, Ludmil B.;Ramakrishna, Manasa;Davies, Helen;Nik-Zainal, Serena;Hardy, Claire;Latimer, Calli;Raine, Keiran M.;Stebbings, Lucy;Menzies, Andy;Jones, David;Shepherd, Rebecca;Butler, Adam P.;Teague, Jon W.;Jorgensen, Mette;Khatri, Bhavisha;Pillay, Nischalan;Shlien, Adam;Futreal, P. Andrew;Badie, Christophe;McDermott, Ultan;Bova, G. Steven;Richardson, Andrea L.;Flanagan, Adrienne M.;Stratton, Michael R.;Campbell, Peter J.
通讯作者：
Campbell, Peter J.
影响因子：
14.9
作者：
Costello M;Pugh TJ;Fennell TJ;Stewart C;Lichtenstein L;Meldrim JC;Fostel JL;Friedrich DC;Perrin D;Dionne D;Kim S;Gabriel SB;Lander ES;Fisher S;Getz G
通讯作者：
Getz G
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y