Abstract
Radiation therapy for thyroid papillary cancer (PTC) rarely induces anaplastic transformation, which shows aggressive behavior. Ret gene rearrangement is a well known molecular alteration observed in PTC and associated with thyroid tumorigenesis. Segmental jumping translocation (SJT) is defined as unbalanced translocations involving a donor chromosome arm or chromosome segment fused to several different recipient chromosomes, suggesting chromosomal instability, and mainly reported in treatment-related leukemia characterized by multiple copies of the ABL oncogenes. While, only a few studies have reported the SJT in solid cancer. In this study, we found Ret SJT in anaplastic thyroid cancer (ATC) induced after radiation therapy for PTC by fluorescence in situ hybridization (FISH). Formalin-fixed paraffin-embedded thyroid tissues from a 44-yo male was used for analyses. He was operated under the diagnosis of PTC and treated by internal radiation with 131I. The tumor recurred at 57-yo and histologically diagnosed as ATC. The FISH analysis demonstrated nuclei showing several Ret signals and two chromosome 10 signals in ATC but not in PTC, suggesting SJT of Ret gene in ATC. The frequency of SJT-positive cells was approximately 30%. PTC showed a wild type Ret signals and neither Ret/PTC1 nor PTC3 by RT-PCR. SJT of Ret may be associated with anaplastic transformation of thyroid cancer after radiation therapy, indicating chromosomal instability.
