Molecular alterations involving p53 codons 167 and 183 in papillary thyroid carcinomas from Chernobyl-contaminated regions of Belarus

After the Chernobyl accident in 1986, there was a significant increase in t he incidence of papillary thyroid carcinoma in fallout-exposed children fro m Belarus. We studied the p53 gene from 24 papillary thyroid carcinoma case s presenting in 1996. All subjects lived in contaminated regions of Belarus at the time of the accident and were under age 20 when exposed to fallout. Exons 5 through 9 of p53 were amplified from genomic tumor DNA using the p olymerase chain reaction (PCR). The PCR products were analyzed by direct DN A sequencing using an automated sequencer. Five cases each exhibited two mo lecular alterations within exon 5. Alterations were confirmed by sequencing in both directions. One alteration, involving codon 167 (CAG --> CAT) in a ll five cases, resulted in the substitution of HIS for GLN. The second alte ration, involving codon 183 (TCA --> TGA) in all five cases, resulted in a premature termination codon. Leukocyte DNA from each of the positive cases was analyzed and found to contain only wild-type p53 sequence. These result s suggest that mutations involving codons 167 and 183 in the p53 locus are important in the pathogenesis of a subset (21%) of radiation-induced papill ary thyroid carcinomas from Belarus.