A radiation-induced gene signature distinguishes post-Chernobyl from sporadic papillary thyroid cancers.
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.
Port
M
M
Bundeswehr Institute of Radiobiology, German Armed Forces, Munich, Germany.
Boltze
C
C
Wang
Y
Y
Röper
B
B
Meineke
V
V
Abend
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002291:Carcinoma, Papillary / Q000145:classification / Q000209:etiology / Q000235:genetics*; D047852:Chernobyl Nuclear Accident; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000528:radiation effects*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000145:classification / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000145:classification / Q000209:etiology / Q000235:genetics*