There are 5 main histological types of thyroid cancers (TCs): papillary, follicular (also known as differentiated), poorly differentiated, anaplastic (the most aggressive form), and medullary TC, and only the latter arises from thyroid C cells. These different forms of TCs show significant variability, both among and within tumours. This great variation is particularly notable among the first 4 types, which all originate from thyroid follicular cells. Importantly, this heterogeneity is not limited to histopathological diversity only but is also manifested as variation in several genetic and/or epigenetic alterations, the numbers of interactions between the tumour and surrounding microenvironment, and interpatient differences, for example. All these factors contribute to the great complexity in the development of a tumour from cancer cells. In the present review, we summarise the knowledge accumulated about the heterogeneity of TCs. Further research in this direction should help to gain a better understanding of the underlying mechanisms contributing to the development and diversity of TCs, paving the way toward more effective treatment strategies.
Background:Papillary thyroid cancer (PTC) incidence increased dramatically in children after the Chernobyl accident, providing a unique opportunity to investigate the molecular features of radiation-induced thyroid cancer. In contrast to the previous studies that included age-related confounding factors, we investigated mRNA expression in PTC and in the normal contralateral tissues of patients exposed and non-exposed to the Chernobyl fallout, using age- and ethnicity-matched non-irradiated cohorts.Methods:Forty-five patients were analysed by full-genome mRNA microarrays. Twenty-two patients have been exposed to the Chernobyl fallout; 23 others were age-matched and resident in the same regions of Ukraine, but were born after 1 March 1987, that is, were not exposed to 131I.Results:A gene expression signature of 793 probes corresponding to 403 genes that permitted differentiation between normal tissues from patients exposed and from those who were not exposed to radiation was identified. The differences were confirmed by quantitative RT-PCR. Many deregulated pathways in the exposed normal tissues are related to cell proliferation.Conclusion:Our results suggest that a higher proliferation rate in normal thyroid could be related to radiation-induced cancer either as a predisposition or as a consequence of radiation. The signature allows the identification of radiation-induced thyroid cancers.
Purpose Following the nuclear accidents in Chernobyl and later in Fukushima, the nuclear community has been faced with important issues concerning how to search for and diagnose biological consequences of low-dose internal radiation contamination. Although after the Chernobyl accident an increase in childhood papillary thyroid cancer (PTC) was observed, it is still not clear whether the molecular biology of PTCs associated with low-dose radiation exposure differs from that of sporadic PTC. Methods We investigated tissue samples from 65 children/ young adults with PTC using DNA microarray (Affymetrix, Human Genome U133 2.0 Plus) with the aim of identifying molecular differences between radiation-induced (exposed to Chernobyl radiation, ECR) and sporadic PTC. All participants were resident in the same region so that confounding factors related to genetics or environment were minimized. Results There were small but significant differences in the gene expression profiles between ECR and non-ECR PTC (global test, p < 0.01), with 300 differently expressed probe sets (p < 0.001) corresponding to 239 genes. Multifactorial analysis of variance showed that besides radiation exposure history, the BRAF mutation exhibited independent effects on the PTC expression profile; the histological subset and patient Daria Handkiewicz-Junak and Michal Swierniak contributed equally to this work.Electronic supplementary material The online version of this article
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