A 30-Year Cytogenetic Follow-Up Study on a Thyroid Cancer Patient after Internal Radioiodine Therapy

Radioiodine (131I) is commonly used for the treatment of hyperthyroidism and for differentiated thyroid cancer as an ablative therapy. Radioiodine (131I) constitutes almost 90% of the therapies that are currently performed in the nuclear medicine field. In this study, retrospective cytogenetic follow-up analysis was performed after 29 years (2023) and 30 years (2024) in a papillary thyroid cancer patient who received the second round of 131I treatment in 1994.

Metaphase chromosomes prepared from the in vitro culture of peripheral blood lymphocytes of the patient were utilized for the analysis of unstable (dicentrics and fragments) and stable chromosome aberrations (simple, complex, and clonal). For dicentric chromosome detection, fluorescence in situ hybridization (FISH) was performed using human centromere- and telomere-specific peptide nucleic acid probes. Chromosome translocations were detected by a cocktail of DNA probes for individual chromosomes (1, 2, and 4) and multicolor FISH (mFISH) probe for the entire human genome. Micronuclei were analyzed by cytokinesis block micronucleus assay (CBMN). Absorbed radiation dose was estimated at 95% confidence intervals from the frequencies of chromosome aberrations (dicentric chromosomes and translocations) using correlation coefficients of the γ-rays dose-response curve using the DoseEstimate_v5.1 algorithm.

The percentage of cells with stable and unstable chromosome aberrations remained the same (∼8%) in the patient during the entire retrospective study albeit variations in the frequencies of reciprocal and nonreciprocal translocations. The frequency of color junctions (chromosome exchange events) detected by the mFISH technique showed a sharp increase in this study (0.33/cell) compared to our earlier study (0.19/cell). The persistence of clonal translocation involving chromosomes 14;15 was observed in 1-1.6% of the total cells analyzed. In the 29-year follow-up study, one complex translocation involving chromosomes 1, 9, and 14 was detected by mFISH in a total of 200 cells.

Our findings indicate that the past internal therapeutic exposure of radioiodine results in long-lasting chromosomal damage and the retrospective study of this nature will be useful for monitoring the progression of any oncogenic events driven by chromosomal instability in the hematopoietic system of 131I therapy patients.