A radiation-induced gene signature distinguishes post-Chernobyl from sporadic papillary thyroid cancers

Radiat Res. 2007 Dec;168(6):639-49. doi: 10.1667/RR0968.1.

Abstract

We investigated selected gene targets to differentiate radiation-induced papillary thyroid cancers (PTCs) from other etiologies. Total RNA was isolated from 11 post-Chernobyl PTCs and 41 sporadic PTCs characterized by a more aggressive tumor type and lacking a radiation exposure history. RNA from 10 tumor samples from both groups was pooled and hybridized separately on a whole genome microarray for screening. Then 92 selected gene targets were examined quantitatively on each tumor sample using an RTQ-PCR-based low-density array (LDA). Screening for more than fivefold differences in gene expression between the groups by microarray detected 646 up-regulated and 677 down-regulated genes. Categorization of these genes revealed a significant (P < 0.0006) over-representation of the number of up-regulated genes coding for oxidoreductases, G-proteins and growth factors, while the number of genes coding for immunoglobulin appeared to be significantly down-regulated. With the LDA, seven genes (SFRP1, MMP1, ESM1, KRTAP2-1, COL13A1, BAALC and PAGE1) made a complete differentiation between the groups possible. Gene expression patterns known to be associated with a more aggressive tumor type in older patients appeared to be more pronounced in post-Chernobyl PTC, thus underlining the known aggressiveness of radiation-induced PTC. Seven genes were found that completely distinguished post-Chernobyl (PTC) from sporadic PTC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Carcinoma, Papillary / classification
  • Carcinoma, Papillary / etiology
  • Carcinoma, Papillary / genetics*
  • Chernobyl Nuclear Accident*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Genome, Human / genetics
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Radiation-Induced / classification
  • Neoplasms, Radiation-Induced / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Sensitivity and Specificity
  • Thyroid Neoplasms / classification
  • Thyroid Neoplasms / etiology
  • Thyroid Neoplasms / genetics*