Microsatellite instability and loss of heterozygosity in radiation-associated thyroid carcinomas of Belarussian children and adults

Abstract

DNA from 129 paired thyroid tumorous and non-tumorous tissue samples of Belarussian children (102 patients; age at surgery </=18 years) and adults (27 patients; age at surgery 19-35 years), who had been exposed to radioactive fallout from the Chernobyl reactor accident in 1986, was examined for microsatellite instability (MSI) and loss of heterozygosity (LOH). Twenty-eight microsatellite markers were chosen because of their vicinity to DNA repair genes or genes involved in tumorigenesis as well as regions of chromosomal breakpoints in thyroid tumours. In 40 patients (31% of 129) we detected a total of 73 alterations, 80% of which were classified as LOH and only 20% as MSI. Amongst these 40 patients we identified a subgroup of 11, mainly young female patients (8.5% of 129), exhibiting alterations in at least two microsatellite markers. For comparison we examined samples from spontaneous thyroid carcinomas without radiation history from 20 adult patients from Munich (mean age at surgery 56 +/- 13 years). None of the tumour samples investigated showed evidence of alterations in the 28 microsatellite markers tested. Taken together our data indicate an increased instability of microsatellite markers in thyroid cancers from Belarussian patients. At present, it is uncertain whether the increased genome instability observed in Belarussian patients is the result of the exposure to radioactive iodine from the Chernobyl reactor accident or due to the young age of the patients.

Genome instability in secondary solid tumors developing after radiotherapy of bilateral retinoblastoma

“…A high rate of microsatellite instability was described in a series of nine tumors secondary to irradiation of pediatric tumors (Gafanovich et al, 1999) and in two series of lung and breast cancers (19 each) after therapy of Hodgkin's disease (radiotherapy plus chemotherapy) (Behrens et al, 2000). In contrast, data from postChernobyl pediatric thyroid carcinomas, suggest that microsatellite instability is not a frequent alteration (Richter et al, 1999). A similar conclusion was drawn for radiation-induced acute myeloid leukemia in the mouse (Richter et al, 1999).…”

“…In contrast, data from postChernobyl pediatric thyroid carcinomas, suggest that microsatellite instability is not a frequent alteration (Richter et al, 1999). A similar conclusion was drawn for radiation-induced acute myeloid leukemia in the mouse (Richter et al, 1999). Cytogenetic data were missing in these studies and it is not possible to establish if in these tumors, the microsatellite instability is associated with a low rate of rearranged chromosomes.…”

“…The three tested minisatellites were found to be stable in the seven analysed tumors. Somatic minisatellite mutations have been detected in several models of radiationinduced tumors (Fennelly et al, 1997 and references herein) and in post-Chernobyl tumors (Richter et al, 1999). In these cases, it was concluded that mutations were not caused directly by radiation-induced DNA damage and that ionizing radiation had a more general indirect eect.…”

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

“…Therefore, it is important to allow for recovery of bone marrow between 131 I treatments. In support of these clinical observations, 131 I has been shown in peripheral lymphocytes to induce a significant increase in the number of dicentric chromosomes (275)(276)(277), and the aberrations of chromosomes 1, 4, and 10 are not only more prevalent but are still apparent after 4 years (276). A recent report comparing thyroid hormone withdrawal to rhTSH suggests a lower frequency of lymphocyte chromosomal rearrangements after 131 I dosing using rhTSH preparation (278).…”

Genetic Events in Radiation-Induced Thyroid Cancer

“…The prevalence of two forms of genome destabilization, somatic mini satellite and microsatellite instability, was tested in postChernobyl papillary thyroid carcinomas. Although several mutations in mini satellite and microsatellite loci was found, the overall prevalence of either type of instability was low (28,29). Loss of heterozygosity (LOR) was seen in very few loci in 6% (28) and 25% (29) of post-Chernobyl papillary carcinomas.…”