Radiation-related genomic profile of papillary thyroid cancer after the Chernobyl accident
The 1986 Chernobyl nuclear power plant accident increased papillary thyroid cancer (PTC) incidence in surrounding regions, particularly for 131 I-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (359 with estimated childhood 131 I exposur...
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| creator | 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, Yosi 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. |
| description | The 1986 Chernobyl nuclear power plant accident increased papillary
thyroid cancer (PTC) incidence in surrounding regions, particularly for
131
I-exposed children. We analyzed genomic, transcriptomic, and
epigenomic characteristics of 440 PTCs from Ukraine (359 with estimated
childhood
131
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 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. |
| doi_str_mv | 10.1126/science.abg2538 |
| format | Article |
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thyroid cancer (PTC) incidence in surrounding regions, particularly for
131
I-exposed children. We analyzed genomic, transcriptomic, and
epigenomic characteristics of 440 PTCs from Ukraine (359 with estimated
childhood
131
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 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.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.abg2538</identifier><identifier>PMID: 33888599</identifier><language>eng</language><ispartof>Science (American Association for the Advancement of Science), 2021-04, Vol.372 (6543)</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids></links><search><creatorcontrib>Morton, Lindsay M.</creatorcontrib><creatorcontrib>Karyadi, Danielle M.</creatorcontrib><creatorcontrib>Stewart, Chip</creatorcontrib><creatorcontrib>Bogdanova, Tetiana I.</creatorcontrib><creatorcontrib>Dawson, Eric T.</creatorcontrib><creatorcontrib>Steinberg, Mia K.</creatorcontrib><creatorcontrib>Dai, Jieqiong</creatorcontrib><creatorcontrib>Hartley, Stephen W.</creatorcontrib><creatorcontrib>Schonfeld, Sara J.</creatorcontrib><creatorcontrib>Sampson, Joshua N.</creatorcontrib><creatorcontrib>Maruvka, Yosi</creatorcontrib><creatorcontrib>Kapoor, Vidushi</creatorcontrib><creatorcontrib>Ramsden, Dale A.</creatorcontrib><creatorcontrib>Carvajal-Garcia, Juan</creatorcontrib><creatorcontrib>Perou, Charles M.</creatorcontrib><creatorcontrib>Parker, Joel S.</creatorcontrib><creatorcontrib>Krznaric, Marko</creatorcontrib><creatorcontrib>Yeager, Meredith</creatorcontrib><creatorcontrib>Boland, Joseph F.</creatorcontrib><creatorcontrib>Hutchinson, Amy</creatorcontrib><creatorcontrib>Hicks, Belynda D.</creatorcontrib><creatorcontrib>Dagnall, Casey L.</creatorcontrib><creatorcontrib>Gastier-Foster, Julie M.</creatorcontrib><creatorcontrib>Bowen, Jay</creatorcontrib><creatorcontrib>Lee, Olivia</creatorcontrib><creatorcontrib>Machiela, Mitchell J.</creatorcontrib><creatorcontrib>Cahoon, Elizabeth K.</creatorcontrib><creatorcontrib>Brenner, Alina V.</creatorcontrib><creatorcontrib>Mabuchi, Kiyohiko</creatorcontrib><creatorcontrib>Drozdovitch, Vladimir</creatorcontrib><creatorcontrib>Masiuk, Sergii</creatorcontrib><creatorcontrib>Chepurny, Mykola</creatorcontrib><creatorcontrib>Zurnadzhy, Liudmyla Yu</creatorcontrib><creatorcontrib>Hatch, Maureen</creatorcontrib><creatorcontrib>de Gonzalez, Amy Berrington</creatorcontrib><creatorcontrib>Thomas, Gerry A.</creatorcontrib><creatorcontrib>Tronko, Mykola D.</creatorcontrib><creatorcontrib>Getz, Gad</creatorcontrib><creatorcontrib>Chanock, Stephen J.</creatorcontrib><title>Radiation-related genomic profile of papillary thyroid cancer after the Chernobyl accident</title><title>Science (American Association for the Advancement of Science)</title><description>The 1986 Chernobyl nuclear power plant accident increased papillary
thyroid cancer (PTC) incidence in surrounding regions, particularly for
131
I-exposed children. We analyzed genomic, transcriptomic, and
epigenomic characteristics of 440 PTCs from Ukraine (359 with estimated
childhood
131
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 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.</description><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqljbFOxDAQRC3EiQscNa1_IIcTK4fd0JxA1OgqGmvjbJJFjm05Bil_jwsaapqZ4o3eMPbQiGPTtKfH1RJ6i0fop7aT6opVjdBdrVshr1klhDzVSjx1e3a7rp9CFKblDdtLqZTqtK7YxzsMBJmCrxM6yDjwCX1YyPKYwkgOeRh5hEjOQdp4nrcUaOAWym3iMOaSeUZ-njH50G-Og7U0oM8HthvBrXj_23fs-fXlcn6r41e_4GDLJIEzMdFSzCYAmb_E02ym8G20aFultPy34AcnnGQs</recordid><startdate>20210422</startdate><enddate>20210422</enddate><creator>Morton, Lindsay M.</creator><creator>Karyadi, Danielle M.</creator><creator>Stewart, Chip</creator><creator>Bogdanova, Tetiana I.</creator><creator>Dawson, Eric T.</creator><creator>Steinberg, Mia K.</creator><creator>Dai, Jieqiong</creator><creator>Hartley, Stephen W.</creator><creator>Schonfeld, Sara J.</creator><creator>Sampson, Joshua N.</creator><creator>Maruvka, Yosi</creator><creator>Kapoor, Vidushi</creator><creator>Ramsden, Dale A.</creator><creator>Carvajal-Garcia, Juan</creator><creator>Perou, Charles M.</creator><creator>Parker, Joel S.</creator><creator>Krznaric, Marko</creator><creator>Yeager, Meredith</creator><creator>Boland, Joseph F.</creator><creator>Hutchinson, Amy</creator><creator>Hicks, Belynda D.</creator><creator>Dagnall, Casey L.</creator><creator>Gastier-Foster, Julie M.</creator><creator>Bowen, Jay</creator><creator>Lee, Olivia</creator><creator>Machiela, Mitchell J.</creator><creator>Cahoon, Elizabeth K.</creator><creator>Brenner, Alina V.</creator><creator>Mabuchi, Kiyohiko</creator><creator>Drozdovitch, Vladimir</creator><creator>Masiuk, Sergii</creator><creator>Chepurny, Mykola</creator><creator>Zurnadzhy, Liudmyla Yu</creator><creator>Hatch, Maureen</creator><creator>de Gonzalez, Amy Berrington</creator><creator>Thomas, Gerry A.</creator><creator>Tronko, Mykola D.</creator><creator>Getz, Gad</creator><creator>Chanock, Stephen J.</creator><scope>5PM</scope></search><sort><creationdate>20210422</creationdate><title>Radiation-related genomic profile of papillary thyroid cancer after the Chernobyl accident</title><author>Morton, Lindsay M. ; 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thyroid cancer (PTC) incidence in surrounding regions, particularly for
131
I-exposed children. We analyzed genomic, transcriptomic, and
epigenomic characteristics of 440 PTCs from Ukraine (359 with estimated
childhood
131
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 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.</abstract><pmid>33888599</pmid><doi>10.1126/science.abg2538</doi></addata></record> |
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| title | Radiation-related genomic profile of papillary thyroid cancer after the Chernobyl accident |
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