Discriminating Gene Expression Signature of Radiation-Induced Thyroid Tumors after Either External Exposure or Internal Contamination

Abstract: Both external radiation exposure and internal radionuclide contamination are well known risk factors in the development of thyroid epithelial tumors. The identification of specific molecular markers deregulated in radiation-induced thyroid tumors is important for the etiological diagnosis since neither histological features nor genetic alterations can discriminate between sporadic and radiation-induced tumors. Identification of highly discriminating markers in radiation-induced tumors is challenging as it relies on the ability to identify marker deregulation which is associated with a cellular stress that occurred many years before in the thyroid cells. The existence of such a signature is still controversial, as it was not found in several studies while a highly discriminating signature was found in both post-radiotherapy and post-Chernobyl series in other studies. Overall, published studies searching for radiation-induced thyroid tumor specificities, using transcriptomic, proteomic and comparative genomic hybridization approaches, and bearing in mind the analytical constraints required to analyze such small series of tumors, suggest that such a molecular signature could be found. In comparison with sporadic tumors, we highlight molecular similarities and specificities in tumors occurring after high-dose external radiation exposure, such as radiotherapy, and in post-Chernobyl tumors that occurred after internal ¹³¹I contamination. We discuss the relevance of signature extrapolation from series of tumors developing after high and low doses in the identification of tumors induced at very low doses of radiation.