THE RET PTC1 ONCOGENE IS ACTIVATED IN FAMILIAL ADENOMATOUS POLYPOSIS-ASSOCIATED THYROID PAPILLARY CARCINOMAS/

Familial adenomatous polyposis (FAP) is caused by germ-line mutations of the ape gene, and it is associated with an increased risk of develo ping papillary thyroid carcinomas. We have previously reported that a significant fraction of sporadic human papillary thyroid carcinomas is characterized by gene rearrangements affecting the ret protooncogene. These rearrangements generate chimeric transforming oncogenes designa ted ret/ptc. By a combined immunohistochemical and RT PCR approach, we analyzed, for ret/ptc oncogene activation, papillary thyroid carcinom as occurred in two FAP kindreds, both showing typical ape gene mutatio ns. Kindred 1 had seven members affected by FAP, and among these, thre e patients showed papillary thyroid carcinomas. Kindred 2 had two pati ents, mother and daughter, affected by colonic polyposis; the 20-yr-ol d daughter showed also a papillary carcinoma. Here we report that ret/ ptc1 oncogene was activated in two of the three papillary carcinomas o f FAP kindred 1 and in the papillary carcinoma of FAP kindred 2. These findings document that loss of function of ape coexists with gain of function of ret in some papillary thyroid carcinomas, suggesting that ret/ptc1 oncogene activation could be a progression step in the develo pment of FAP-associated thyroid tumors.