Thyroidectomies from patients with history of therapeutic radiation during childhood and adolescence have a unique mutational profile

Department of Pathology, Virginia Mason Medical Center, Seattle, WA, USA.
Modern Pathology (Impact Factor: 6.19). 07/2008; 21(9):1176-82. DOI: 10.1038/modpathol.2008.122
Source: PubMed


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.

5 Reads
  • Guy's Hospital reports 02/1969; 118(3):353-61.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Radiation exposure at a young age is the only environmental factor known to cause thyroid cancer, predominantly of the papillary type. We have previously reported a high percentage (86.7%) of RET-positive papillary thyroid cancers in a cohort of individuals exposed to external radiation of the head and neck area before the age of 16. Recently, we and others have reported that point mutations of the BRAF gene occur with high frequency among sporadic adult papillary thyroid carcinomas, but occur at a much lower frequency in the population exposed after the Chernobyl accident. We here report that there is a similar low frequency of BRAF mutations among our cohort of those exposed to external beam radiation as children who later developed papillary thyroid cancer as adults. Samples were analyzed by mutation allele-specific amplification (MASA) for the most common T1799A mutation in exon 15 that converts amino acid 600 from valine to glutamate. In 23 cases, only 1 sample was positive. These results are further evidence that BRAF mutations, while common in sporadic adult papillary thyroid cancers, are rare events in cancers seen in subjects exposed to radiation as children.
    Thyroid 02/2006; 16(1):61-6. DOI:10.1089/thy.2006.16.61 · 4.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid and parathyroid diseases are fairly common and can be either hereditary or sporadic in nature. Tumors and tumor-like processes account for the majority of surgical pathology specimens in both of these endocrine organs. Molecular alterations are well known to occur in both the hereditary and the sporadic settings, and include alterations in tumor suppressor genes and oncogenes. The genetic pathways of tumors of parathyroid and thyroid are beginning to be well understood and are proving to be useful diagnostic, prognostic, and potential therapeutic targets. The molecular alterations in parathyroid and thyroid tumors and tumor-like processes are reviewed, with a focus on the potentially clinically useful diagnostic markers.
    Advances in anatomic pathology 02/2009; 16(1):23-32. DOI:10.1097/PAP.0b013e3181915f7d · 3.23 Impact Factor
Show more


5 Reads
Available from