PREVALENCE OF MUTATIONS OF RAS AND P53 IN BENIGN AND MALIGNANT THYROID-TUMORS FROM CHILDREN EXPOSED TO RADIATION AFTER THE CHERNOBYL NUCLEAR ACCIDENT

Starting 4 years after the Chernobyl accident, a dramatic increase in incidence of thyroid carcinoma was noticed in children from contaminat ed areas, The incidence of benign thyroid lesions in the exposed popul ation was also increased, To study the possible role of ras and p53 ge nes in radiation-induced thyroid tumorigenesis, 33 papillary carcinoma s, one follicular carcinoma and 22 benign lesions removed from childre n aged 5-19 were screened for point mutations of H- K-, and N-ras, as well as of p53 (exons 5-8) using single strand conformation polymorphi sm (SSCP) analysis, Pas point mutations were detected in 1/1 case of f ollicular carcinoma (N-ras codon 61 CAA(gln)-->AAA(lys)), and in 3/7 f ollicular adenomas (N-ras codon 61 CAA(gin)-->CGA(arg) x 2, CAA(gln)-- >AAA(lys). None of the cases of papillary thyroid carcinoma was positi ve for ras oncogene abnormalities, The lack of K-ras mutations was con firmed by allele-specific oligonucleotide hybridization (ASOH), and by sequencing in five cases, Somatic point mutations in p53 were found b y SSCP in 2/33 papillary thyroid carcinomas, with one missense mutatio n (exon 5, codon 160 ATG(met)-->GTG(val)) and another silent mutation (codon 182, TGC(cys)-->TGT(cys)). Immunohistochemically, focally posit ive p53 staining was found in four papillary carcinomas being primaril y confined to solid and poorly-differentiate areas in tumors, These da ta demonstrate that as opposed to the few reports on tumors arising af ter therapeutic external irradiation, ras mutations are not primary ev ents in the development of post-Chernobyl thyroid papillary carcinomas , p53 mutations do not appear to be important in the development of th ese tumors, but may in some cases have a role in progression to a more aggressive phenotype that has not yet fully manifested in these pedia tric neoplasms.