Mutations in the RET protooncogene cause familial cases of medullary thyroid cancer, which in some cases coexists with pheochromocytoma and primary hyperparathyreoidism as the MEN2A syndrome.
Aim of the study: Evaluation of frequency of pheochromocytomas and their clinical course in the RET protooncogene mutations carriers.
Material: One hundred and seventy nine patients, among them 109 probands and 70 family members in whom RET germinal mutations were detected. 90 probands had DNA analysis because of diagnosis of medullary thyroid cancer and 19 because of pheochromocytoma.
Methods: Analyzed DNA was isolated from peripheral blood leukocytes. Exons 10, 11, 13, 14, 15 and 16 were analyzed. From the beginning exons 10, 13, 14, 15 and 16 were analyzed with the use of direct DNA sequencing, and since 2007 also exon 11, which previously was analyzed with the use of RFLP.
Results: The frequency of pheochromocytoma/paraganglioma in the mutations carriers was 29% (n=51). Multiple lesions present at the time of diagnosis or occurring during follow-up were present in 34 cases (66%). In 3 cases malignant tumors were diagnosed. According to the type of mutation pheochromocytomas were present in 1/1 cases with codon 534 mutation, 1/1 cases with codon 609 mutation, 1/3 cases with codon 611 mutation, 2/17 cases with codon 618 mutation, 0/9 cases with codon 620 mutation, 33/66 cases with codon 634 mutations, 0/6 cases with codon 768 mutation,0/4 cases with codon 790 mutation, 6/30 cases with codon 791 mutation, 0/14 cases with codon 804 mutation, 1/7 cases with codon 891 mutation and 4/14 cases with codon 918 mutation.
Conclusions: Pheochromocytomas are present in about 1/3 of RET mutations carriers and in majority of cases are multiple and benign tumors located in adrenal medulla. Their frequency depends on the type of mutation and only in patients with codon 634 mutations is up to 50%.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology