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Discriminating Gene Expression Signature of Radiation-Induced Thyroid Tumors after Either External Exposure or Internal Contamination
CEA, DSV, IRCM, SREIT, Laboratoire de Cancérologie Expérimentale, BP6, Fontenay-aux-Roses, F-92265, France
Institut Gustave Roussy, Department on Nuclear Medicine and Endocrine Oncology, Villejuif, and University Paris-Sud, F-94800, France
INSERM ERI-21, Nice, F-06002, France
University of Nice-Sophia Antipolis, IFR 50, Nice, F-06002, France
Laboratory of Clinical and Experimental Pathology and CHU-CRLCC-UNSA tumour tissue bank of Nice area, Louis Pasteur Hospital, Nice, F-06002, France
* Author to whom correspondence should be addressed.
Received: 3 November 2011; in revised form: 6 December 2011 / Accepted: 9 December 2011 / Published: 21 December 2011
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.
Keywords: thyroid; radiation-induced tumors; transcriptomic signature; molecular epidemiology
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Ory, C.; Ugolin, N.; Schlumberger, M.; Hofman, P.; Chevillard, S. Discriminating Gene Expression Signature of Radiation-Induced Thyroid Tumors after Either External Exposure or Internal Contamination. Genes 2012, 3, 19-34.
Ory C, Ugolin N, Schlumberger M, Hofman P, Chevillard S. Discriminating Gene Expression Signature of Radiation-Induced Thyroid Tumors after Either External Exposure or Internal Contamination. Genes. 2012; 3(1):19-34.
Ory, Catherine; Ugolin, Nicolas; Schlumberger, Martin; Hofman, Paul; Chevillard, Sylvie. 2012. "Discriminating Gene Expression Signature of Radiation-Induced Thyroid Tumors after Either External Exposure or Internal Contamination." Genes 3, no. 1: 19-34.