title: Comparison of transcriptomic signature of post-Chernobyl and postradiotherapy thyroid tumors.
abstract: BACKGROUND
  We previously identified two highly discriminating and predictive radiation-induced transcriptomic signatures by comparing series of sporadic and postradiotherapy thyroid tumors (322-gene signature), and by reanalyzing a previously published data set of sporadic and post-Chernobyl thyroid tumors (106-gene signature). The aim of the present work was (i) to compare the two signatures in terms of gene expression deregulations and molecular features/pathways, and (ii) to test the capacity of the postradiotherapy signature in classifying the post-Chernobyl series of tumors and reciprocally of the post-Chernobyl signature in classifying the postradiotherapy-induced tumors.
  
  
  METHODS
  We now explored if postradiotherapy and post-Chernobyl papillary thyroid carcinomas (PTC) display common molecular features by comparing molecular pathways deregulated in the two tumor series, and tested the potential of gene subsets of the postradiotherapy signature to classify the post-Chernobyl series (14 sporadic and 12 post-Chernobyl PTC), and reciprocally of gene subsets of the post-Chernobyl signature to classify the postradiotherapy series (15 sporadic and 12 postradiotherapy PTC), by using conventional principal component analysis.
  
  
  RESULTS
  We found that the five genes common to the two signatures classified the learning/training tumors (used to search these signatures) of both the postradiotherapy (seven PTC) and the post-Chernobyl (six PTC) thyroid tumor series as compared with the sporadic tumors (seven sporadic PTC in each series). Importantly, these five genes were also effective for classifying independent series of postradiotherapy (five PTC) and post-Chernobyl (six PTC) tumors compared to independent series of sporadic tumors (eight PTC and six PTC respectively; testing tumors). Moreover, part of each postradiotherapy (32 genes) and post-Chernobyl signature (16 genes) cross-classified the respective series of thyroid tumors. Finally, several molecular pathways deregulated in post-Chernobyl tumors matched those found to be deregulated in postradiotherapy tumors.
  
  
  CONCLUSIONS
  Overall, our data suggest that thyroid tumors that developed following either external exposure or internal (131)I contamination shared common molecular features, related to DNA repair, oxidative and endoplasmic reticulum stresses, allowing their classification as radiation-induced tumors in comparison with sporadic counterparts, independently of doses and dose rates, which suggests there may be a "general" radiation-induced signature of thyroid tumors.
authors.affiliation: 1 Laboratory of Experimental Oncology, Institute of Cellular and Molecular Radiation Biology (IRCM), Directorate of Life Sciences (DSV), Commission for Atomic Energy and Alternative Energies (CEA), Fontenay-aux-Roses, France .
authors.forename: Catherine
authors.initials: C
authors.lastname: Ory
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ugolin
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Illya A
authors.initials: IA
authors.lastname: Likhtarev
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevillard
mesh_terms: D000293:Adolescent; D000328:Adult; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D002291:Carcinoma, Papillary; D047852:Chernobyl Nuclear Accident; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair; D004190:Disasters; D059865:Endoplasmic Reticulum Stress; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D007223:Infant; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D025341:Principal Component Analysis; D011878:Radiotherapy / Q000379:methods; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D007457:Iodine Radioisotopes