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 contaminated areas. The incidence of benign thyroid lesions in the exposed population was also increased. To study the possible role of ras and p53 genes in radiation-induced thyroid tumorigenesis, 33 papillary carcinomas, one follicular carcinoma and 22 benign lesions removed from children 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 polymorphism (SSCP) analysis. Ras point mutations were detected in 1/1 case of follicular carcinoma (N-ras codon 61 CAAgln-->AAAlys), and in 3/7 follicular adenomas (N-ras codon 61 CAAgln-->CGAarg x 2, CAAgln-->AAAlys). None of the cases of papillary thyroid carcinoma was positive for ras oncogene abnormalities. The lack of K-ras mutations was confirmed by allele-specific oligonucleotide hybridization (ASOH), and by sequencing in five cases. Somatic point mutations in p53 were found by SSCP in 2/33 papillary thyroid carcinomas, with one missense mutation (exon 5, codon 160 ATGmet-->GTGval) and another silent mutation (codon 182, TGCcys-->TGTcys). Immunohisto-chemically, focally positive p53 staining was found in four papillary carcinomas being primarily confined to solid and poorly-differentiated areas in tumors. These data demonstrate that as opposed to the few reports on tumors arising after therapeutic external irradiation, ras mutations are not primary events in the development of post-Chernobyl thyroid papillary carcinomas. p53 mutations do not appear to be important in the development of these tumors, but may in some cases have a role in progression to a more aggressive phenotype that has not yet fully manifested in these pediatric neoplasms.
Nikiforov
Y E
YE
Division of Endocrinology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Nikiforova
M N
MN
Gnepp
D R
DR
Fagin
J A
JA
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D017931:DNA Primers; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011210:Power Plants; D018788:Radioactive Hazard Release; D013964:Thyroid Neoplasms / Q000235:genetics*; D014455:Ukraine
D017931:DNA Primers