title: Gene expression signature discriminates sporadic from post-radiotherapy-induced thyroid tumors.
abstract: Both external and internal exposure to ionizing radiation are strong risk factors for the development of thyroid tumors. Until now, the diagnosis of radiation-induced thyroid tumors has been deduced from a network of arguments taken together with the individual history of radiation exposure. Neither the histological features nor the genetic alterations observed in these tumors have been shown to be specific fingerprints of an exposure to radiation. The aim of our work is to define ionizing radiation-related molecular specificities in a series of secondary thyroid tumors developed in the radiation field of patients treated by radiotherapy. To identify molecular markers that could represent a radiation-induction signature, we compared 25K microarray transcriptome profiles of a learning set of 28 thyroid tumors, which comprised 14 follicular thyroid adenomas (FTA) and 14 papillary thyroid carcinomas (PTC), either sporadic or consecutive to external radiotherapy in childhood. We identified a signature composed of 322 genes which discriminates radiation-induced tumors (FTA and PTC) from their sporadic counterparts. The robustness of this signature was further confirmed by blind case-by-case classification of an independent set of 29 tumors (16 FTA and 13 PTC). After the histology code break by the clinicians, 26/29 tumors were well classified regarding tumor etiology, 1 was undetermined, and 2 were misclassified. Our results help shed light on radiation-induced thyroid carcinogenesis, since specific molecular pathways are deregulated in radiation-induced tumors.
authors.affiliation: CEA, DSV, IRCM, LCE, BP6, Fontenay-aux-Roses F-92265, France. catherine.ory@cea.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Ory
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ugolin
authors.forename: Céline
authors.initials: C
authors.lastname: Levalois
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.forename: Bernard
authors.initials: B
authors.lastname: Caillou
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bidart
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.forename: Ibrahima
authors.initials: I
authors.lastname: Diallo
authors.forename: Florent
authors.initials: F
authors.lastname: de Vathaire
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
authors.forename: José
authors.initials: J
authors.lastname: Santini
authors.forename: Bernard
authors.initials: B
authors.lastname: Malfoy
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevillard
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011878:Radiotherapy / Q000009:adverse effects*; D011879:Radiotherapy Dosage; D016037:Single-Blind Method; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins