Translocation t(10;14)(q11.2;q22.1) fusing the kinectin to the RET gene creates a novel rearranged form (PTC8) of the RET proto-oncogene in radiationinduced childhood papillary thyroid carcinoma

Evaluation of 20 cases of radiation-induced childhood papillary thyroid car cinoma using fluorescence in situ hybridization demonstrated the presence o f clonal translocations affecting the RET locus. Semiquantitative reverse t ranscription-PCR indicated overexpression of the RET tyrosine kinase (TK) d omain in four cases. In two cases, the RET rearrangements PTC6 and PTC7 wer e identified and assigned to balanced translocations t(7;10)(q32;q11.2) and t(1;10)(p13;q11.2), respectively. In one case with a balanced translocatio n t(10;14)(q11.2;q22.1), 5' rapid amplification of cDNA ends revealed a nov el type of RET oncogenic activation (PTC8), arising from a fusion of the 5' part of the kinectin (KTN1) gene to the TK domain of the RET gene. The pre sence of coiled-coil domains in the resulting ktn1/ret fusion protein sugge sts ligand-independent dimerization and thus constitutive activation of the ret TK domain.