A gene expression signature distinguishes normal tissues of sporadic and radiation-induced papillary thyroid carcinomas

Br J Cancer. 2012 Sep 4;107(6):994-1000. doi: 10.1038/bjc.2012.302. Epub 2012 Jul 24.

Abstract

Background: Papillary thyroid cancer (PTC) incidence increased dramatically in children after the Chernobyl accident, providing a unique opportunity to investigate the molecular features of radiation-induced thyroid cancer. In contrast to the previous studies that included age-related confounding factors, we investigated mRNA expression in PTC and in the normal contralateral tissues of patients exposed and non-exposed to the Chernobyl fallout, using age- and ethnicity-matched non-irradiated cohorts.

Methods: Forty-five patients were analysed by full-genome mRNA microarrays. Twenty-two patients have been exposed to the Chernobyl fallout; 23 others were age-matched and resident in the same regions of Ukraine, but were born after 1 March 1987, that is, were not exposed to ¹³¹I.

Results: A gene expression signature of 793 probes corresponding to 403 genes that permitted differentiation between normal tissues from patients exposed and from those who were not exposed to radiation was identified. The differences were confirmed by quantitative RT-PCR. Many deregulated pathways in the exposed normal tissues are related to cell proliferation.

Conclusion: Our results suggest that a higher proliferation rate in normal thyroid could be related to radiation-induced cancer either as a predisposition or as a consequence of radiation. The signature allows the identification of radiation-induced thyroid cancers.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / analysis*
  • Carcinoma
  • Carcinoma, Papillary
  • Chernobyl Nuclear Accident*
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Diet
  • Disease Susceptibility
  • Gene Expression Profiling*
  • Humans
  • Infant
  • Iodine / administration & dosage
  • Iodine / deficiency
  • Neoplasms, Radiation-Induced / chemistry*
  • Neoplasms, Radiation-Induced / diagnosis
  • Neoplasms, Radiation-Induced / epidemiology
  • Neoplasms, Radiation-Induced / genetics
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Cancer, Papillary
  • Thyroid Gland / chemistry*
  • Thyroid Gland / radiation effects
  • Thyroid Neoplasms / chemistry*
  • Thyroid Neoplasms / diagnosis
  • Thyroid Neoplasms / epidemiology
  • Thyroid Neoplasms / etiology
  • Thyroid Neoplasms / genetics
  • Thyrotropin / metabolism
  • Transcriptome
  • Ukraine / epidemiology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Thyrotropin
  • Iodine