| Literature DB >> 33888599 |
Lindsay M Morton1, Danielle M Karyadi2, Chip Stewart3, Tetiana I Bogdanova4, Eric T Dawson2,5, Mia K Steinberg6, Jieqiong Dai6, Stephen W Hartley2, Sara J Schonfeld7, Joshua N Sampson8, Yosef E Maruvka3, Vidushi Kapoor6, Dale A Ramsden9, Juan Carvajal-Garcia10, Charles M Perou11,12, Joel S Parker12, Marko Krznaric13, Meredith Yeager6, Joseph F Boland6, Amy Hutchinson6, Belynda D Hicks6, Casey L Dagnall6, Julie M Gastier-Foster14,15, Jay Bowen14, Olivia Lee2, Mitchell J Machiela16, Elizabeth K Cahoon7, Alina V Brenner17, Kiyohiko Mabuchi7, Vladimir Drozdovitch7, Sergii Masiuk18, Mykola Chepurny18, Liudmyla Yu Zurnadzhy4, Maureen Hatch7, Amy Berrington de Gonzalez7, Gerry A Thomas13, Mykola D Tronko19, Gad Getz3,20,21, Stephen J Chanock22.
Abstract
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.Entities:
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Year: 2021 PMID： 33888599 PMCID： PMC9022889 DOI： 10.1126/science.abg2538
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 63.714