Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident

被引：93

作者：

Morton, Lindsay M. ^{[1
]}

Karyadi, Danielle M. ^{[2
]}

Stewart, Chip ^{[3
]}

Bogdanova, Tetiana, I ^{[4
]}

Dawson, Eric T. ^{[2
,5
]}

Steinberg, Mia K. ^{[6
]}

Dai, Jieqiong ^{[6
]}

Hartley, Stephen W. ^{[2
]}

Schonfeld, Sara J. ^{[1
]}

Sampson, Joshua N. ^{[7
]}

Maruvka, Yosef E. ^{[3
]}

Kapoor, Vidushi ^{[6
]}

Ramsden, Dale A. ^{[8
]}

Carvajal-Garcia, Juan ^{[9
]}

Perou, Charles M. ^{[10
,11
]}

Parker, Joel S. ^{[11
]}

Krznaric, Marko ^{[12
]}

Yeager, Meredith ^{[6
]}

Boland, Joseph F. ^{[6
]}

Hutchinson, Amy ^{[6
]}

Hicks, Belynda D. ^{[6
]}

Dagnall, Casey L. ^{[6
]}

Gastier-Foster, Julie M. ^{[13
,14
,15
]}

Bowen, Jay ^{[13
]}

Lee, Olivia ^{[2
]}

Machiela, Mitchell J. ^{[16
]}

Cahoon, Elizabeth K. ^{[1
]}

Brenner, Alina, V ^{[17
]}

Mabuchi, Kiyohiko ^{[1
]}

Drozdovitch, Vladimir ^{[1
]}

Masiuk, Sergii ^{[18
]}

Chepurny, Mykola ^{[18
]}

Zurnadzhy, Liudmyla Yu ^{[4
]}

Hatch, Maureen ^{[1
]}

de Gonzalez, Amy Berrington ^{[1
]}

Thomas, Gerry A. ^{[12
]}

Tronko, Mykola D. ^{[19
]}

Getz, Gad ^{[3
,20
,21
]}

Chanock, Stephen J. ^{[2
]}

机构：

[1] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[2] NCI, Lab Genet Susceptibil, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] Natl Acad Med Sci Ukraine, Lab Morphol Endocrine Syst, VP Komisarenko Inst Endocrinol & Metab, UA-04114 Kiev, Ukraine

[5] Nvidia Corp, Santa Clara, CA 95051 USA

[6] Leidos Biomed Res Inc, Canc Genom Res Lab, Frederick Natl Lab Canc Res, Bethesda, MD 20892 USA

[7] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[8] Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[9] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA

[10] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[11] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[12] Imperial Coll London, Charing Cross Hosp, Dept Surg & Canc, London W6 8RF, England

[13] Nationwide Childrens Hosp, Biospecimen Core Resource, Columbus, OH 43205 USA

[14] Ohio State Univ, Dept Pathol, Coll Med, Columbus, OH 43210 USA

[15] Ohio State Univ, Dept Pediat, Coll Med, Columbus, OH 43210 USA

[16] NCI, Integrat Tumor Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA

[17] Radiat Effects Res Fdn, Hiroshima 7320815, Japan

[18] Natl Acad Med Sci Ukraine, Inst Radiat Hyg & Epidemiol, Radiol Protect Lab, Natl Res Ctr Radiat Med, UA-04050 Kiev, Ukraine

[19] Natl Acad Med Sci Ukraine, Dept Fundamental & Appl Problems Endocrinol, VP Komisarenko Inst Endocrinol & Metab, UA-04114 Kiev, Ukraine

[20] Massachusetts Gen Hosp, Ctr Canc Res & Dept Pathol, Boston, MA 02114 USA

[21] Harvard Med Sch, Boston, MA 02115 USA

来源：

SCIENCE | 2021年 / 372卷 / 6543期

基金：

美国国家卫生研究院;

关键词：

MUTATIONAL SIGNATURES; CANCER RISK; IONIZING-RADIATION; EXTERNAL RADIATION; POOLED ANALYSIS; DISCOVERY; EXPOSURE; PROGRAM; FUSION; AGE;

D O I：

10.1126/science.abg2538

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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

引用

页码：705 / +

页数：55

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