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. 2016 Jul;43(7):1267-77.
doi: 10.1007/s00259-015-3303-3. Epub 2016 Jan 26.

Gene signature of the post-Chernobyl papillary thyroid cancer

Daria Handkiewicz-Junak  1 , Michal Swierniak  1   2 , Dagmara Rusinek  1 , Małgorzata Oczko-Wojciechowska  1 , Genevieve Dom  3 , Carine Maenhaut  3 , Kristian Unger  4   5 , Vincent Detours  3 , Tetiana Bogdanova  6 , Geraldine Thomas  4 , Ilya Likhtarov  7 , Roman Jaksik  8 , Malgorzata Kowalska  1 , Ewa Chmielik  9 , Michal Jarzab  10 , Andrzej Swierniak  11 , Barbara Jarzab  12
Affiliations

Gene signature of the post-Chernobyl papillary thyroid cancer

Daria Handkiewicz-Junak et al. Eur J Nucl Med Mol Imaging. 2016 Jul.

Abstract

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 age at diagnosis had negligible effects. Ten genes (PPME1, HDAC11, SOCS7, CIC, THRA, ERBB2, PPP1R9A, HDGF, RAD51AP1, and CDK1) from the 19 investigated with quantitative RT-PCR were confirmed as being associated with radiation exposure in an independent, validation set of samples.

Conclusion: Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure.

Keywords: Adolescents; Children; Gene expression; Papillary thyroid cancer; Radiation; Transcriptome.

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Figures

Fig. 1
Fig. 1
Multidimensional scaling of samples. Samples coloured red are ECR tumours, green are non-ECR tumours, blue are ECR normal thyroids, and cyan are non-ECR normal thyroids
Fig. 2
Fig. 2
Genes validated in the qPCR study
See this image and copyright information in PMC

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