Segmental Jumping Translocation of Ret Oncogene in Radiation-associated Thyroid Cancer

DOI 機関リポジトリ HANDLE
  • NAKASHIMA Masahiro
    Tissue and Histopathology Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences
  • TAKAMURA Noboru
    Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences
  • NAMBA Hiroyuki
    Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences
  • SAENKO Vladimir
    Department of International Health and Radiation Research, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences
  • HAYASHI Tomayoshi
    Department of Pathology, Nagasaki University Hospital
  • SEKINE Ichiro
    Tissue and Histopathology Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences

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Radiation etiology is well known in thyroid carcinogenesis. Ret rearrangement is the commonest oncogenic alterations in Chernobyl-related papillary thyroid cancer (PTC). To evaluate whether there is a radiation signature, we analyzed Ret rearrangement in radiation-associated thyroid cancers with fluorescence in situ hybridization (FISH) and reverse transcriptase-polymerase chain reaction (RT-PCR). The FISH analysis demonstrated segmental jumping translocation (SJT) of Ret gene in radiation-associated thyroid cancers but not in sporadic well differentiated PTC. Furthermore, Ret SJT was commonly observed in anaplastic thyroid cancer (ATC) including both radiation-associated and sporadic cancers. In PTC, Ret SJT was restricted to radiation-associated or high-grade cases. Because Ret SJT was not observed in sporadic, well differentiated and low-grade cases of PTC, Ret SJT might be a molecular marker for radiation-induced and/or aggressive cases of PTC. SJTs are unbalanced translocations involving a donor chromosome arm or chromosome segment that has fused to multiple recipient chromosome, and mainly reported in treatment-related leukemias, while very rare in solid cancers. We found SJT in radiation-induced and high-grade thyroid cancers, suggesting chromosomal instability. This is the first report showing SJT in thyroid cancer, and probably the third report showing SJT in solid cancer in vivo.

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