ABSENCE OF MUTATIONS IN THE MEN2A REGION OF THE RET PROTOONCOGENE IN NON-MEN 2A PHEOCHROMOCYTOMAS

OBJECTIVE To determine the presence of abnormalities of the MEN2A regi on of the rot proto-oncogene in phaeochromocytomas/paragangliomas (PHA EO) of different aetiologies. DESIGN Total RNA was extracted from tumo urs and used as templates for reverse transcriptase polymerase chain r eactions. A ret primer pair, which encompasses the region which is mut ated in the germ-line of patients with MEN 2A, was used. The resulting 262-bp product was sequenced. PATIENTS Ten PHAEOs were examined. Four tumours were from von Hippel-Lindau disease patients; five were spora dic, isolated tumours; one from a patient with multiple endocrine neop lasia type 2A (MEN 2A). The medullary thyroid cancer from the single M EN 2A patient was also examined. RESULTS A heterozygous TGC to CGC mut ation of codon 634 (cysteine to arginine) was found in the PHAEO and m edullary thyroid cancer from the MEN 2A patient. The 262-bp ret fragme nt was not found in two tumours (one malignant PHAEO and one secretory paraganglioma), although the intra-cellular rot tyrosine kinase domai n was detected in these tumours. The cysteine codons were normal In al l other non-MEN 2A PHAEOs. CONCLUSION Mutations of key cysteine codons of the let proto-oncogene may be specific to MEN 2A.