title: Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers.
abstract: 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.
authors: 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
authors: V
authors: V
authors: Detours
authors: L
authors: L
authors: Delys
authors: F
authors: F
authors: Libert
authors: D
authors: D
authors: Weiss Solís
authors: T
authors: T
authors: Bogdanova
authors: J E
authors: JE
authors: Dumont
authors: B
authors: B
authors: Franc
authors: G
authors: G
authors: Thomas
authors: C
authors: C
authors: Maenhaut
mesh_terms: 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
chemical_list: D006861:Hydrogen Peroxide
references: Thyroid. 2000 Dec;10(12):1126-7
references: 11201862
references: Cancer Res. 1997 May 1;57(9):1690-4
references: 9135009
references: Int J Epidemiol. 2004 Oct;33(5):1025-33
references: 15166190
references: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4168-72
references: 12642676
references: Bioinformatics. 2005 Jan 15;21(2):171-8
references: 15308542
references: Nat Rev Genet. 2006 Jan;7(1):55-65
references: 16369572
references: Mol Cell Endocrinol. 2006 Sep 26;257-258:6-14
references: 16859826
references: Clin Endocrinol (Oxf). 1989 Dec;31(6):655-65
references: 2627756
references: Endocr Pathol. 2002 Spring;13(1):3-16
references: 12114746
references: Lancet. 2003 Nov 1;362(9394):1439-44
references: 14602436
references: Endocrinology. 1997 Jan;138(1):369-78
references: 8977426
references: Thyroid. 2005 Feb;15(2):94-9
references: 15753665
references: Oncogene. 2003 Jul 17;22(29):4578-80
references: 12881714
references: Cancer Res. 2005 Feb 15;65(4):1587-97
references: 15735049
references: Mutat Res. 2005 Sep 4;577(1-2):275-83
references: 15922366
references: Nature. 1992 Sep 3;359(6390):21-2
references: 1522880
references: Int J Radiat Biol. 2000 Jan;76(1):67-75
references: 10665959
references: Diagn Cytopathol. 2001 Oct;25(4):231-4
references: 11599106
references: J Clin Endocrinol Metab. 2005 Apr;90(4):2364-9
references: 15671095
references: Endocr Relat Cancer. 2005 Jun;12(2):245-62
references: 15947100
references: Br J Cancer. 2005 Apr 25;92(8):1545-52
references: 15812549
references: Proc Natl Acad Sci U S A. 2002 May 14;99(10):6567-72
references: 12011421
references: J Clin Endocrinol Metab. 1994 Jul;79(1):152-9
references: 8027219
references: Oncogene. 2005 Oct 6;24(44):6646-56
references: 16007166
references: Stat Appl Genet Mol Biol. 2004;3:Article37
references: 16646817
references: Clin Sci (Lond). 2006 Jul;111(1):1-20
references: 16764554
references: Nature. 2003 Jul 31;424(6948):561-5
references: 12891360
references: Cancer Res. 1996 Nov 1;56(21):4846-52
references: 8895731
references: Oncogene. 2005 Jun 30;24(28):4572-9
references: 15824734
references: Lancet. 2005 Feb 5-11;365(9458):488-92
references: 15705458
references: Endocr Rev. 2005 Dec;26(7):944-84
references: 16174820
references: Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6062-7
references: 15075390
references: J Clin Endocrinol Metab. 2004 Sep;89(9):4280-4
references: 15356022
references: Mod Pathol. 2005 Jul;18(7):898-902
references: 15968271
references: Science. 2001 Feb 16;291(5507):1284-9
references: 11181991
references: Cancer Lett. 2004 Jun 8;209(1):1-6
references: 15145515
references: Acta Cytol. 2005 Jul-Aug;49(4):378-82
references: 16124165
references: Am J Physiol Endocrinol Metab. 2000 Apr;278(4):E692-9
references: 10751204
references: Cancer Res. 2003 Apr 1;63(7):1454-7
references: 12670889
references: J Pathol. 2005 Apr;205(5):558-64
references: 15714593
references: Laryngoscope. 2005 Jun;115(6):938-45
references: 15933498
references: Mutat Res. 2003 Jan 28;522(1-2):21-6
references: 12517408
references: N Engl J Med. 2004 Oct 21;351(17):1764-71
references: 15496625
references: Oncogene. 2004 Sep 23;23(44):7436-40
references: 15273715
references: Oncol Rep. 2006 Apr;15(4):949-56
references: 16525684
references: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references: 11309499
references: Br J Cancer. 2004 Jun 1;90(11):2219-24
references: 15150580
references: DNA Repair (Amst). 2002 Jun 21;1(6):483-93
references: 12509235
references: J Clin Endocrinol Metab. 2004 Sep;89(9):4267-71
references: 15356020
references: Proc Natl Acad Sci U S A. 2002 May 14;99(10):6562-6
references: 11983868
references: Nature. 1992 Sep 3;359(6390):21
references: 1522879
references: J Natl Cancer Inst. 2003 Jan 1;95(1):14-8
references: 12509396
references: Cancer Res. 2006 Oct 15;66(20):9845-51
references: 17047045