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

Clin Cancer Res. 2000 Mar;6(3):1093-103.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / pathology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dose-Response Relationship, Radiation
  • Drosophila Proteins*
  • Female
  • Gene Rearrangement / radiation effects
  • Genetic Variation
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Neoplasm Staging
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / pathology
  • Phenotype
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ret
  • Radioactive Hazard Release*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, trkA / genetics*
  • Sex Factors
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Time Factors

Substances

  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkA
  • Ret protein, Drosophila