Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers.
Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n=12) and from French patients with no history of exposure to ionising radiations (n=14). We also compared the transcriptional responses of human lymphocytes to the presumed aetiological agents initiating these tumours, gamma-radiation and H(2)O(2). On a global scale, the transcriptomes of CTB and French tumours are indistinguishable, and the transcriptional responses to gamma-radiation and H(2)O(2) are similar. On a finer scale, a 118 genes signature discriminated the gamma-radiation and H(2)O(2) responses. This signature could be used to classify the tumours as CTB or French with an error of 15-27%. Similar results were obtained with an independent signature of 13 genes involved in homologous recombination. Although sporadic and radio-induced PTCs represent the same disease, they are distinguishable with molecular signatures reflecting specific responses to gamma-radiation and H(2)O(2). These signatures in PTCs could reflect the susceptibility profiles of the patients, suggesting the feasibility of a radiation susceptibility test.
Detours
V
V
Institute of Interdisciplinary Research, School of Medicine, Univertisté Libre de Bruxelles (ULB), Campus Erasme, CP602, route de Lennik 808, Brussels, Belgium. vdetours@ulb.ac.be
Delys
L
L
Libert
F
F
Weiss Solís
D
D
Bogdanova
T
T
Dumont
J E
JE
Franc
B
B
Thomas
G
G
Maenhaut
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002291:Carcinoma, Papillary / Q000209:etiology / Q000235:genetics*; D047852:Chernobyl Nuclear Accident; D002648:Child; D002675:Child, Preschool; D005260:Female; D005602:France; D005720:Gamma Rays / Q000009:adverse effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D006861:Hydrogen Peroxide / Q000009:adverse effects; D007223:Infant; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011832:Radiation Injuries / Q000150:complications / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics*; D014015:Tissue Banks; D014158:Transcription, Genetic / Q000187:drug effects / Q000528:radiation effects
D006861:Hydrogen Peroxide
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