Pattern of radiation-induced RET and NTRK1 rearrangements in 191 post-Chernobyl papillary thyroid carcinomas: Biological, phenotypic, and clinical implications

Molecular genetic aberrations and the related phenotypes were investigated in 191 papillary thyroid carcinomas (PTCs) from patients exposed at young a ge to radioiodine released from the Chernobyl reactor. A high prevalence of RET gene rearrangements (62.3%) with a significant predominance of ELE1/RE T (PTC3) over H4/RET (PTC1) rearrangements was found in PTCs of the first p ost-Chernobyl decade, NTRK1 rearrangements were rare (3.3%), In 3.3%, we ob served novel types of RET rearrangements: GOLGA5/ RET (PTC5), HTIF/RET (PTC 6), 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 rearr angements 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 ELE 1/RET was observed in the most heavily contaminated Oblasts, Gomel and Bres t, suggesting a preferential formation of this type of rearrangement after high thyroid doses. RET rearrangement is related to aggressive growth: Rear rangement-positive PTCs were in a more advanced pT category and more freque ntly in the pN(1) category at presentation than rearrangement-negative PTCs , ELE1/RET is related to the solid variant of PTC, H4/RET more frequently t o typical papillary structures, The genotype/phenotype evaluation of post-C hernobyl PTCs reveals a characteristic spectrum of gene rearrangements that lead to typical phenotypes with important biological and clinical implicat ions.