ONCOGENIC REARRANGEMENTS OF THE RET PROTOONCOGENE IN THYROID-TUMORS INDUCED AFTER EXPOSURE TO IONIZING-RADIATION

A high frequency (approximate to 60%) of ret rearrangements in Chernob yl papillary thyroid carcinomas (PTC) has been reported recently. The data suggested that the radiation exposure may be a direct inducer of activating rearrangements in the rct gene. In our study, we have analy zed for the presence of RET/PTC oncogenes using the RT-PCR, XL-PCR. So uthern blot and direct sequencing techniques, 39 human thyroid tumors from patients who had received external radiation for benign or malign ant conditions. As controls, we studied 39 'spontaneous' tumors. Our r esults indicate that: 1) the overall frequency of ret rearrangements w as 84% in papillary carcinomas (16/19) and 45% (9/20) in follicular ad enomas; 2) in contrast with the results obtained in the Chernobyl tumo rs, the most frequently observed chimeric gene was RET/PTC1; and 3) al l the tumors were negative for RET/PTC2. In the 'spontaneous' tumors, only the papillary carcinomas presented a ret rearrangement (15%: 3/20 ). Our data confirm the crucial role played by the ret proto-oncogene activating rearrangements in the development of radiation-associated t hyroid tumors, and show, for the first time, the presence of RET/PTC g enes in follicular adenomas appeared after external irradiation.