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 with other genes is a frequent finding in papillary thyroid carcinoma. The tk domain of proto‐RET can be fused either with the D10S170 gene generating the RET/PTCI transforming sequence or with sequences belonging to the gene encoding the regulatory subunit R/A of c‐AMP‐dependent protein kinase A, thus forming the RET/PTC2 oncogene. We have previously shown that an inversion of chromosome 10, inv(10)(q11.2q21), is responsible for the generation of the RET/PTCI. Here we report that a chromosomal translocation, t(10;17)(q11.2;q23), juxtaposes the tk domain of the RET protooncogene, which resides on chromosome 10, to a 5′ portion of the R/A gene on chromosome 17, leading to the formation of the chimeric transforming gene RET/PTC2. The finding of the transforming protein in primary tumor cell extracts supports the conclusion that RET/PTC2 activation plays a role in papillary thyroid tumorigenesis.