Fusion of a novel gene, ELKS, to RET due to translocation t(10;12)(q11;p13) in a papillary thyroid carcinoma

In papillary thyroid carcinomas, the genes for receptor-type tyrosine kinas e, RET or TRKA, are sometimes rearranged, resulting in fusion of its tyrosi ne kinase domain to 5' portions of several activating genes. In a papillary thyroid carcinoma, we identified a novel gene (ELKS), the 5' portion of wh ich is fused to the RET gene by gene rearrangement due to the translocation t(10; 12)(q 11;p 13). Subsequent cloning of the ELKS cDNA revealed that EL KS encodes a novel 948 amino acid peptide and is expressed ubiquitously in human tissues. The presence of multiple coiled-coil domains in the ELKS pro duct suggests that the ELKS protein forms dimers. Since the tyrosine kinase of RET is activated by dimerization that occurs when its ligands bind to t he receptor, fusion of RET with the 5' dimerization domains of ELKS would a ctivate its cytoplasmic tyrosine kinase constitutively in papillary thyroid carcinomas. (C) 1999 Wiley-Liss, Inc.