A T(10 17) TRANSLOCATION CREATES THE RET/PTC2 CHIMERIC TRANSFORMING SEQUENCE IN PAPILLARY THYROID-CARCINOMA/

Activation of the RET protooncogene tyrosine kinase (tk) by fusion wit h other genes is a frequent finding in papillary thyroid carcinoma. Th e tk domain of proto-RET can be fused either with the D10S170 gene gen erating the RET/PTC1 transforming sequence or with sequences belonging to the gene encoding the regulatory subunit RIA of c-AMP-dependent pr otein kinase A, thus forming the RET/PTC2 oncogene. We have previously shown that an inversion of chromosome 10, inv(10)(q11.2q21), is respo nsible for the generation of the RET/PTC1. Here we report that a chrom osomal translocation, t(10;17)(q11.2;q23), juxtaposes the tk domain of the RET protooncogene, which resides on chromosome 10, to a 5' portio n of the RIA gene on chromosome 17, leading to the formation of the ch imeric transforming gene RET/PTC2. The finding of the transforming pro tein in primary tumor cell extracts supports the conclusion that RET/P TC2 activation plays a role in papillary thyroid tumorigenesis. (C) 19 94 Wiley-Liss, Inc.