Gene signature of the post-Chernobyl papillary thyroid cancer.
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.
['Handkiewicz-Junak|Daria|D|', 'Swierniak|Michal|M|', 'Rusinek|Dagmara|D|', 'Oczko-Wojciechowska|Małgorzata|M|', 'Dom|Genevieve|G|', 'Maenhaut|Carine|C|', 'Unger|Kristian|K|', 'Detours|Vincent|V|', 'Bogdanova|Tetiana|T|', 'Thomas|Geraldine|G|', 'Likhtarov|Ilya|I|', 'Jaksik|Roman|R|', 'Kowalska|Malgorzata|M|', 'Chmielik|Ewa|E|', 'Jarzab|Michal|M|', 'Swierniak|Andrzej|A|', 'Jarzab|Barbara|B|']
D000293:Adolescent D000328:Adult D002277:Carcinoma D002291:Carcinoma, Papillary D002648:Child D002675:Child, Preschool D005091:Exons D005260:Female D020869:Gene Expression Profiling D006801:Humans D007223:Infant D007231:Infant, Newborn D008297:Male D009381:Neoplasms, Radiation-Induced D016133:Polymerase Chain Reaction D018788:Radioactive Hazard Release D000077273:Thyroid Cancer, Papillary D013964:Thyroid Neoplasms D055815:Young Adult
Papillary thyroid cancer Radiation Children Gene expression Adolescents Transcriptome