Distinctive molecular features of radiation-induced thyroid cancers
Papillary thyroid carcinoma (PTC) incidence increased after childhood exposure to radioactive fallout from the Chornobyl accident. We investigated PTC genomic profiles to distinguish radiation-induced versus sporadic oncogenic drivers by modeling dose and molecular characteristics by driver category: <i>BRAF<sup>V600E</sup></i> (<i>n</i> = 132), RAS mutation (<i>n</i> = 31), fusions generated from two breakpoints and <20 base pairs (bp) breakpoint gain/loss (Fusion<sup>2B<20bp</sup>; <i>n</i> = 63), or ≥3 breakpoints and ≥1000 bp breakpoint loss (<i>n</i> = 20). The frequency of Fusion<sup>2B<20bp</sup>-PTC increased with increasing thyroid radiation dose, whereas all others declined. Clonal small deletion counts increased with increasing radiation dose for Fusion<sup>2B<20bp</sup>-PTC (<i>P</i> = 5.1 × 10<sup>-4</sup>) but not other drivers (<i>P</i> > 0.08). Clonal clock mutational signatures, marking the age of tumor initiation, were associated with age at the accident for Fusion<sup>2B<20bp</sup>-PTC (<i>P</i> = 8.2 × 10<sup>-4</sup>) but not other drivers (<i>P</i> > 0.21). Together, these results support a causal role for ionizing radiation in Fusion<sup>2B<20bp</sup>-PTC as a group but not other drivers.
Authors
- Lindsay McOmber Morton (ORCID: https://orcid.org/0000-0001-9767-2310)
- Gayle E. Woloschak
- Mykola Chepurny (ORCID: https://orcid.org/0000-0001-9852-0669)
- М.D. Тronko (ORCID: https://orcid.org/0000-0001-7421-0981)
- Caitlin M. Milder (ORCID: https://orcid.org/0000-0002-9400-2095)
- Liudmyla Zurnadzhy
- Vibha Vij (ORCID: https://orcid.org/0000-0002-1411-0257)
- Cari M. Kitahara (ORCID: https://orcid.org/0000-0001-6416-4432)
- Danielle M. Karyadi (ORCID: https://orcid.org/0000-0003-4164-5625)
- Elizabeth K. Cahoon (ORCID: https://orcid.org/0000-0002-8028-0588)
- Stephen W. Hartley (ORCID: https://orcid.org/0000-0001-6584-005X)
- Olivia W. Lee (ORCID: https://orcid.org/0000-0001-5389-6267)
- Michael Dean (ORCID: https://orcid.org/0000-0003-2234-0631)
- Sergii Masiuk (ORCID: https://orcid.org/0000-0002-5123-9674)
- Bogdanova Ti (ORCID: https://orcid.org/0000-0001-5119-0236)
- Dale A. Ramsden (ORCID: https://orcid.org/0000-0003-1575-4748)
- Vladimir Drozdovitch (ORCID: https://orcid.org/0000-0002-7952-379X)
- Stephen J. Chanock (ORCID: https://orcid.org/0000-0002-2324-3393)
- Gerry Thomas
Institutions
- Northwestern University (US)
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- Charing Cross Hospital (GB)
- V.P. Komisarenko Institute of Endocrinology and Metabolism (UA)
- National Cancer Institute (US)
- National Academy of Medical Sciences of Ukraine (UA)
- Imperial College London (GB)
Publication Details
- Journal
- Science Advances
- Published
- 2025-08-22
- DOI
- https://doi.org/10.1126/sciadv.adw7680
- Citations
- 1
- Primary Topic
- Thyroid Cancer Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.29