MULTIPLE ENDOCRINE NEOPLASIA TYPE 2-ASSOCIATED RET PROTOONCOGENE MUTATIONS DO NOT CONTRIBUTE TO THE PATHOGENESIS OF SPORADIC PARATHYROID TUMORS

Background. Parathyroid disease occurs sporadically or as part of here ditary multiple endocrine neoplasia (MEN) syndrome. The aim of this st udy was to evaluate the possible role of the RET proto-oncogene not on ly in hereditary MEN 2-associated hyperparathyroidism but also in diff erent forms of sporadic hyperparathyroidism. Methods. We investigated 22 patients with parathyroid disease whose family history and results of laboratory and clinical examination excluded MEN 2 syndrome. DNA ex tractions of histologically confirmed tumor tissue of patients with pr imary hyperparathyroidism (n = 18), renal hyperparathyroidism (n = 2), and parathyroid carcinoma (n = 2) were performed. Using solid Phase D NA sequencing, mutation analysis of polymerase chain reaction amplifie d products focuses on exons 10, 11, and 16 of the RET proto-oncogene. Parathyroid tissue from four patients with known MEN 2A saved as posit ive controls. Results. No mutations of the codons 609, 611, 618, 620 6 34, and 918 were found In the sporadic parathyroid tumors analyzed. DN A sequencing revealed heterozygous mutations in codon 634 of the RET p roto-oncogene in four parathyroid glands from four patients with MEN 2 A. Conclusions. Mutations of the RET proto-oncogene contributing to ME N 2 syndromes are absent in sporadic parathyroid tumors. Our data in c onjunction with the literature suggest at least three different modes of tumorigenesis in parathyroid disease.