ALTERATIONS OF RET ONCOGENE IN HUMAN ADRENAL-TUMORS

Previous studies have revealed specific activations of the RET oncogen e in multiple endocrine neoplasia type 2 (MEN 2) and thyroid tumors. T o understand the role of the RET proto oncogene activation in sporadic adrenal tumors, we analyzed the alterations of the RET proto-oncogene in the cysteine-rich extracellular domain (exons 6 and 10), the termi nal region of the extracellular domain and transmembrane domain (exon 11) and the tyrosine kinase domain (exons 12-17) in 35 cases of adrena l tumors (including 18 Conn's syndrome, 3 Gushing's syndrome, 2 non fu nctional adrenocortical tumor and 12 pheochromocytomas by polymerase c hain reaction-single strand conformational polymorphism and sequencing methods. One case with pheochromocytoma and one with Gonn's syndrome had point mutation. We also detected the rearrangement of the RET gene by reverse transcription-polymerase chain reaction and Southern hybri dization, One case with Gonn's syndrome and one with Gushing's syndrom e mere found to harbor RET/PTC1 (RET tyrosine kinase domain rearranged with H4 gene). The above results indicate that RET protooncogene muta tions and RET/PTC1 are involved in the pathogenesis of sporadic adrena l tumors. Mutations at codon 634 of the RET gene were also found in ad renal tumors. This suggests that the RET oncogene may also play a role in the tumorigenesis of adrenal tumors, and this possibility requires further investigation.