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

Science. 2021 May 14;372(6543):eabg2538. doi: 10.1126/science.abg2538. Epub 2021 Apr 22.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Chernobyl Nuclear Accident*
  • Child
  • Child, Preschool
  • DNA Copy Number Variations
  • Epigenome
  • Female
  • Gene Expression Profiling
  • Genes, ras
  • Genetic Variation
  • Humans
  • Infant
  • Iodine Radioisotopes
  • Loss of Heterozygosity
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasms, Radiation-Induced / genetics*
  • Proto-Oncogene Proteins B-raf / genetics
  • RNA-Seq
  • Radiation Dosage
  • Thyroid Cancer, Papillary / etiology*
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Gland / physiology
  • Thyroid Gland / radiation effects
  • Thyroid Neoplasms / etiology*
  • Thyroid Neoplasms / genetics*
  • Translocation, Genetic
  • Ukraine
  • Whole Genome Sequencing
  • Young Adult


  • Iodine Radioisotopes
  • Iodine-131
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf