RADIATION-INDUCED POST-CHERNOBYL PEDIATRIC THYROID CARCINOMAS

Exposure to ionizing radiation induces different forms of genomic inst ability in cultured cells and experimental animals. A higher rate of g ermline mutations at human hypervariable minisatellite loci was report ed in children born from parents exposed to radiation after Chernobyl, implicating genome destabilization as a possible mechanism responsibl e for late radiation effects in humans. To test if radiation-induced c arcinogenesis in the thyroid gland may be associated with somatic mini satellite instability or microsatellite instability, we utilized a PCR -based approach to study normal and tumor DNA from 17 pediatric post-C hernobyl papillary thyroid carcinomas for mutations at three different minisatellite loci (D1S80, D17S30, ApoB), and 27 microsatellite loci of di-, tri-, or tetranucleotide repeats. Minisatellite instability wa s found in three (18%) tumors, with one of them exhibiting mutations i n all three minisatellite loci, whereas two others showed mutations in one of two informative markers. By contrast, none of 20 sporadic thyr oid cancers from patients with no history of radiation exposure was po sitive for minisatellite instability. Microsatellite analysis of post- Chernobyl tumors revealed a mutation in one (6%) tumor only at the loc us of D10S1412, whereas all other 26 microsatellite markers showed ide ntical patterns in each normal/tumor pair. Our results suggest that so matic cell microsatellite instability does not contribute to radiation -induced thyroid carcinogenesis. However, somatic minisatellite mutati on events are present in a subset of radiation-induced, but not sporad ic, thyroid cancers, suggesting that this type of genomic instability may play a role in radiation-induced tumorigenesis in the thyroid glan d.