RET rearrangements in papillary thyroid carcinomas and adenomas detected by interphase FISH

Activation of the RET protooncogene through somatic rearrangements represen ts the most common genetic alteration in papillary thyroid carcinoma (PTC), Three main rearranged forms of RET have been described: RET/PTC1 and RET/P TC3, which arise from a paracentric inversion of the long arm of chromosome 10, and RET/PTC2, which originates from a 10;17 translocation. We have dev eloped a dual-color FISH approach to detect RET/PTC rearrangements in inter phase nuclei of thyroid lesions. By using a pool of three cosmids encompass ing the RET chromosome region and a chromosome 10 centromeric probe, we cou ld discriminate between the presence of an inversion (RET/PTC1 and RET/PTC3 ) or a translocation (RET/PTC2). We have investigated a series of thyroid t issue samples from Italian and French patients corresponding to a total of 69 PTCs and 22 benign lesions. Among PTCs, 13 (18.8 %) showed a RET rearran gement, and 11 (15.9 %) of these carried an inversion (RET/PTC1 or RET/PTC3 ) in more than 10% of the nuclei examined. Activated forms of RET were also observed in three adenomas. RT-PCR analysis on the same samples confirmed the presence and the type of rearrangement predicted using FISH analysis. A n interesting difference in the frequency and type of RET rearrangements wa s detected between the Italian and the French patients. Furthermore, we ide ntified a putative novel type of rearrangement in at least one PTC sample. Several PTCs carried a significant number of cells characterized by a triso my or a tetrasomy of chromosome 10. Overall, the FISH approach in interphas e nuclei represents a powerful tool for detecting, at the single cell level , RET/PTC rearrangements and other anomalies involving the RET chromosome r egion. Copyright (C) 2000 S. Karger AG, Basel.