ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 3.1 | DOI: 10.1530/ey.18.3.1

Science. 2021;372(6543):eabg2538. doi: 10.1126/science.abg2538.

Radioactive iodine (131I)-exposed children in the region of Chernobyl (Ukraine) showed an increased incidence of papillary thyroid carcinoma (PTC) after the 1986 nuclear plant accident [1]. This so far the largest and most comprehensive study to characterize the genomic landscape of radiation induced PTC in a large number of tissues from the Chernobyl Tissue Bank originating from a precisely phenotyped cohort of 131I exposed patients. The findings reveal DNA damage as early driver of carcinogenesis and lack of a unique molecular signature for radiation induced PTC.

To investigate the dose-dependent contribution of 131I-related radiation on carcinogenesis of PTC, Morton et al. performed a genomic, transcriptomic, and epigenomic analysis of PTC and normal thyroid tissue in 359 radiation exposed vs. 81 non-radiation exposed patients with PTC. Mean estimated radiation dose to the thyroid was 250 mGy (range 11-8800). The authors describe three key observations: First, they observed a linear radiation dose-dependent increase in DNA double strand breaks as an early event during carcinogenesis. Second, in >90% of PTC, they found a known tumor driver in the mitogen-activated protein kinase (MAPK) pathway, such as mutations in BRAF, RAS, and fusions with RET in accordance with current knowledge on sporadic PTC [2]. Third, gene expression and methylation patterns were not associated with radiation dose but correlated with the affected driver gene pathway. Thus, no molecular pattern of PTC after radiation exposure could be identified.

Reference: 1. Tronko M, Brenner AV, Bogdanova T, Shpak V, Oliynyk V, Cahoon EK, Drozdovitch V, Little MP, Tereshchenko V, Zamotayeva G, Terekhova G, Zurnadzhi L, Hatch M, Mabuchi K. Thyroid neoplasia risk is increased nearly 30 years after the Chernobyl accident. Int J Cancer. 2017;141:1585–1588. doi: 10.1002/ijc.30857.2. Cancer Genome Atlas Research Network Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159:676–90. doi: 10.1016/j.cell.2014.09.050.

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