title: Gene signature of the post-Chernobyl papillary thyroid cancer.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Significant, but subtle, differences in gene expression in the post-Chernobyl PTC are associated with previous low-dose radiation exposure.
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland.
authors.forename: Daria
authors.initials: D
authors.lastname: Handkiewicz-Junak
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland.|Genomic Medicine, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Swierniak
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Rusinek
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Oczko-Wojciechowska
authors.affiliation: Institute of Interdisciplinary Research, Université libre de Bruxelles (ULB), Bruxelles, Belgium.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Dom
authors.affiliation: Institute of Interdisciplinary Research, Université libre de Bruxelles (ULB), Bruxelles, Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Maenhaut
authors.affiliation: Human Cancer Studies Group, Division of Surgery and Cancer, Imperial College London Hammersmith Hospital, London, UK.|Research Unit Radiation Cytogenetics, Helmholtz-Zentrum, Munich, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Unger
authors.affiliation: Institute of Interdisciplinary Research, Université libre de Bruxelles (ULB), Bruxelles, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Detours
authors.affiliation: Institute of Endocrinology and Metabolism, Kiev, Ukraine.
authors.forename: Tetiana
authors.initials: T
authors.lastname: Bogdanova
authors.affiliation: Human Cancer Studies Group, Division of Surgery and Cancer, Imperial College London Hammersmith Hospital, London, UK.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Thomas
authors.affiliation: Radiation Protection Institute, Academy of Technological Sciences of Ukraine, Kiev, Ukraine.
authors.forename: Ilya
authors.initials: I
authors.lastname: Likhtarov
authors.affiliation: Systems Engineering Group, Faculty of Automatic Control, Electronics and Informatics, Silesian University of Technology, Gliwice, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Jaksik
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kowalska
authors.affiliation: Department of Tumour Pathology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Chmielik
authors.affiliation: IIIrd Department of Radiation Therapy, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Jarzab
authors.affiliation: Department of Automatic Control, Silesian University of Technology, Gliwice, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Swierniak
authors.affiliation: Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland. Barbara.Jarzab@io.gliwice.pl.
authors.forename: Barbara
authors.initials: B
authors.lastname: Jarzab
mesh_terms: D000293:Adolescent; D000328:Adult; D002277:Carcinoma / Q000209:etiology* / Q000235:genetics*; D002291:Carcinoma, Papillary; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018788:Radioactive Hazard Release; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000235:genetics*; D055815:Young Adult
keywords: Adolescents; Children; Gene expression; Papillary thyroid cancer; Radiation; Transcriptome
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