title: Thyroidectomies from patients with history of therapeutic radiation during childhood and adolescence have a unique mutational profile.
abstract: Radiation in childhood is a known risk factor for thyroid carcinoma, but may also be related to benign nodular hyperplasias. Recent evidence from comparative genomic hybridization indicates that radiation can induce clonal DNA damage in cultured rat thyrocytes. We used a loss of heterozygosity analysis for the loci identified by comparative genomic hybridization to study human thyroids. Thyroids from patients with a history of radiation, patients who had recent therapeutic external beam radiation for laryngeal carcinoma, and patients who had no radiation and underwent incidental thyroidectomy with laryngectomy for laryngeal carcinoma were included. PCR was performed for 18 different genetic loci defined by prior reported comparative genomic hybridization study. A semiquantitative capillary electrophoresis analysis was used and frequency of allelic loss was calculated from the number of losses/the number of informative loci. A total of 40 cases of thyroids from patients with childhood radiation, 12 cases of recently radiated thyroids, and 15 cases of nonradiated thyroids were included. In the nonradiated and recently radiated thyroids, the mean frequency of allelic loss was 2.3%. In the thyroids from patients radiated as children, the mean frequency of allelic loss was 39%. Losses were seen at every locus with a range of 7-100% of the cases analyzed (mean 49.6%). Radiation in childhood was associated with both benign nodular disease and carcinomas of the thyroid. The frequency of allelic loss was very high in all lesions in these patients, as compared to control thyroid glands. These data from human thyroids support prior cell culture experiments and show that radiation induces genetic mutational damage even in benign proliferative processes in these thyroids.
authors.affiliation: Department of Pathology, Virginia Mason Medical Center, Seattle, WA, USA.
authors.forename: Adel
authors.initials: A
authors.lastname: Assaad
authors.forename: Laura
authors.initials: L
authors.lastname: Voeghtly
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hunt
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000209:etiology / Q000235:genetics / Q000601:surgery; D000236:Adenoma / Q000209:etiology / Q000235:genetics / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000532:radiotherapy*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics* / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf