biostudies-literatureUnknown11(34)Karyadi DMPapillary 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: BRAFV600E (n = 132), RAS mutation (n = 31), fusions generated from two breakpoints and <20 base pairs (bp) breakpoint gain/loss (Fusion2B<20bp; n = 63), or ≥3 breakpoints and ≥1000 bp breakpoint loss (n = 20). The frequency of Fusion2B<20bp-PTC increased with increasing thyroid radiation dose, whereas all others declined. Clonal small deletion counts increased with increasing radiation dose for Fusion2B<20bp-PTC (P = 5.1 × 10-4) but not other drivers (P > 0.08). Clonal clock mutational signatures, marking the age of tumor initiation, were associated with age at the accident for Fusion2B<20bp-PTC (P = 8.2 × 10-4) but not other drivers (P > 0.21). Together, these results support a causal role for ionizing radiation in Fusion2B<20bp-PTC as a group but not other drivers.Science advanceseadw7680https://www.ebi.ac.uk/biostudies/studies/S-EPMC12372901biostudies-literatureDistinctive molecular features of radiation-induced thyroid cancers.PMC12372901Bogdanova TIVij VKaryadi DMMasiuk SChanock SJMorton LMKitahara CMRamsden DAZurnadzhy LYTronko MDLee OWChepurny MMilder CMDrozdovitch VWoloschak GEThomas GACahoon EKDean MHartley SWfalseDistinctive 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: BRAFV600E (n = 132), RAS mutation (n = 31), fusions generated from two breakpoints and <20 base pairs (bp) breakpoint gain/loss (Fusion2B<20bp; n = 63), or ≥3 breakpoints and ≥1000 bp breakpoint loss (n = 20). The frequency of Fusion2B<20bp-PTC increased with increasing thyroid radiation dose, whereas all others declined. Clonal small deletion counts increased with increasing radiation dose for Fusion2B<20bp-PTC (P = 5.1 × 10-4) but not other drivers (P > 0.08). Clonal clock mutational signatures, marking the age of tumor initiation, were associated with age at the accident for Fusion2B<20bp-PTC (P = 8.2 × 10-4) but not other drivers (P > 0.21). Together, these results support a causal role for ionizing radiation in Fusion2B<20bp-PTC as a group but not other drivers.2025-01-01T00:00:00Z2025 Aug2026-05-08T10:48:11.147Z2026-04-07T23:47:50.14ZS-EPMC123729014084511710.1126/sciadv.adw7680