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Molecular Oncology, Markers, Clinical Correlates |
Institute of Pathology, Ludwig-Maximilians-University, D-80337 Munich, Germany [H. M. R., C. B., S. K.]; Thyroid Cancer Center, 220600 Minsk, Belarus [E. P. D., J. D. S.]; Institute of Radiation Biology Ludwig-Maximilians-University, D-80336 Munich, Germany [E. L.]; Department of Medical Informatics, Biometry and Epidemiology, University of Munich, D-81377 Munich, Germany [D. H.]
Molecular genetic aberrations and the related phenotypes were investigated in 191 papillary thyroid carcinomas (PTCs) from patients exposed at young age to radioiodine released from the Chernobyl reactor. A high prevalence of RET gene rearrangements (62.3%) with a significant predominance of ELE1/RET (PTC3) over H4/RET (PTC1) rearrangements was found in PTCs of the first post-Chernobyl decade. NTRK1 rearrangements were rare (3.3%). In 3.3%, we observed novel types of RET rearrangements: GOLGA5/RET (PTC5), HTIF/RET (PTC6), RFG7/RET (PTC7), and an as yet undefined RFGX/RET. RET rearrangements, preferentially ELE1/RET, are related to rapid tumor development. At longer intervals after exposure to ionizing radiation, the prevalence of RET rearrangements declines with a shift from ELE1/RET to H4/RET, most significantly in female patients. The prevalence of specific types of rearrangements is independent of age at irradiation. A significantly higher prevalence of ELE1/RET was observed in the most heavily contaminated Oblasts, Gomel and Brest, suggesting a preferential formation of this type of rearrangement after high thyroid doses. RET rearrangement is related to aggressive growth: Rearrangement-positive PTCs were in a more advanced pT category and more frequently in the pN1 category at presentation than rearrangement-negative PTCs. ELE1/RET is related to the solid variant of PTC, H4/RET more frequently to typical papillary structures. The genotype/phenotype evaluation of post-Chernobyl PTCs reveals a characteristic spectrum of gene rearrangements that lead to typical phenotypes with important biological and clinical implications.
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