RET oncogene amplification in thyroid cancer: Correlations with radiation-associated, high-grade malignancy, and genomic instability

.RET oncogene rearrangement is a well-known molecular alteration observed in papillary thyroid cancer (PTC). RET rearrangement is the commonest oncogenic alterations in Chernobyl-related PTC; nearly all to RET/PTC1 or RET/PTC3, resulting from paracentric inversion of chromosome 10. Other less common variants, usually forming as a result of interchromosomal translocation, occur in an extremely limited number of cases. Most often such translocations have been found in radiation-induced PTC. Here, we report the presence of RET oncogene amplification, a new type of RET cytogenetic alteration, in human thyroid cancers. RET amplification was correlated with radiation-associated, high-grade malignant potency, and p53 overexpression, suggesting genomic instability. We also examined p53-binding protein 1 (53BP1) expressions with immunostaining to clarify the presence of genomic instability in thyroid cancers. In thyroid tumors, the level of 53BP1-focus formation was associated with malignant transformation and high-grade malignant potency as well as RET amplification. RET amplification might be induced by a high level of genomic instability with progression of thyroid carcinogenesis and, subsequently, be associated with radiation-induced and/or high-grade malignant cases.