RET is expressed but not mutated in extra-adrenal paragangliomas

This study has investigated the role of the RET proto-oncogene, which has b een identified as the susceptibility gene for multiple endocrine neoplasia (MEN) type 2, in the development of sporadic and familial extra-adrenal par agangliomas. RET protein expression was analysed by immunohistochemistry. S ubsequently, DNA extracted from 52 tumours of 44 patients was screened for somatic RET point mutations in exons 10, 11, and 13-16, where ontogenic mut ations have recently been described in a subset of sporadic medullary thyro id carcinomas and phaeochromocytomas. The methods employed included non-iso topic polymerase chain reaction-based single strand conformation polymorphi sm (PCR-SSCP) analysis and heteroduplex gel electrophoresis, followed by di rect sequencing of PCR products. RET protein expression was demonstrated in all ten paragangliomas tested. However, none of the familial or sporadic e xtra-adrenal paragangliomas contained somatic mutations in exons 10, 11, or 13-16 of the RET proto-oncogene, whereas control samples with known mutati ons in these exons exhibited the expected band shift, or yielded an additio nal band,vith retarded migration. Although paragangliomas exhibit RET prote in expression, these data indicate that oncogenic RET proto-oncogene mutati ons do not appear to he generally important in the formation of sporadic pa ragangliomas. Copyright (C) 2000 John Wiley & Sons, Ltd.