This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Igaz, P. Articles by Ésik, O. Search for Related Content PubMed Articles by Igaz, P. Articles by Ésik, O.

Occurrence of Pheochromocytoma in a MEN2A Family with Codon 609 Mutation of the RET Protooncogene

Second Department of Medicine (P.I., A.P., K.R.), Faculty of Medicine, Semmelweis University, 1088 Budapest, Hungary; Institute of Enzymology of the Hungarian Academy of Sciences (I.K., A.V.), 1113 Budapest, Hungary; and Department of Radiotherapy (O.E.), Semmelweis University and National Institute of Oncology, 1122 Budapest, Hungary

Address correspondence to: Károly Rácz, M.D., Ph.D., D.Sc., Second Department of Medicine, Faculty of Medicine, Semmelweis University, 1088 Budapest, Szentkirályi strasse 46, Hungary. E-mail: . racz{at}bel2.sote.hu

To the editor:

In their recent paper, Brandi et al. (1) reviewed the currently available data for the diagnosis and therapy of MEN syndrome types 1 and 2. In the section dealing with the screening for tumor expression in MEN2 carriers, they state that pheochromocytoma has not been found in MEN2 kindreds harboring codon 609 (exon 10) mutations of the RET proto-oncogene. In a previous study, Eng et al. (2) came to the same conclusion.

We have found a MEN2A family harboring a codon 609 mutation in which the index patient was operated for an adrenal pheochromocytoma at the age of 48 yr. Subsequent endocrinological investigation revealed a highly elevated basal serum calcitonin level (780 pg/ml; normal, <11.5 pg/ml). Fine needle aspiration cytology from a thyroid nodule was consistent with medullary thyroid carcinoma (MTC). Total thyroidectomy was performed, and the histological examination of the thyroid verified the MTC.

Molecular examination of the DNA extracted from the proband’s blood showed a codon 609 mutation (TGC609TCC, Cys609Ser at the amino acid level) (3). The same mutation was verified in two independent laboratories, from two independent blood samples. To our knowledge, this type of mutation at codon 609 has not been reported previously.

The family history of the patient seemed particularly interesting. Two decades earlier, the mother of the proband was operated for an adrenal pheochromocytoma at the age of 50 yr. A few months later, MTC was diagnosed, and the patient underwent thyroidectomy. The patient died of metastatic pheochromocytoma in the same year. Unfortunately, tissue sample has not been available for genetic analysis.

The son of the proband was diagnosed to harbor the codon 609 mutation, and prophylactic thyroidectomy was performed at the age of 14 yr. Screening for pheochromocytoma has been negative. The other two children of the index patient were negative for the mutation.

In summary, in this MEN2A family with codon 609 mutation of the RET proto-oncogene two members had pheochromocytoma. It appears that these two members of the family are the first reported cases in whom pheochromocytoma was associated with a codon 609 mutation. In addition, the TGC609TTC seems to be a novel RET exon 10 mutation.

Received February 12, 2002.

References

1. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJM, Lombardi G, Mannelli M, Pacini F, Ponder BAJ, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA, Marx SJ 2001 Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 86:5658–5671[Abstract/Free Full Text]
2. Eng C, Clayton D, Schuffenecker I, Lenoir G, Cote G, Gagel RF, Ploos van Amstel HK, Lips CJM, Nishisho I, Takai SI, Marsh DJ, Robinson BG, Frank-Raue K, Raue F, Xu F, Noll WW, Romei C, Pacini F, Fink M, Niederle B, Zedenius J, Nordenskjöld M, Komminoth P, Hendy G, Gharib H, Thibodeau S, Lacroix A, Frilling A, Ponder BAJ, Mulligan LM 1996 The relationship between specific RET proto-oncogene mutations and disease genotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 276:1575–1579[Abstract/Free Full Text]
3. Klein I, Ésik O, Homolya V, Szeri F, Váradi A 2001 Molecular genetic diagnostic program of multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma syndromas in Hungary. J Endocrinol 170:661–666[Abstract]

This article has been cited by other articles:

				R. Asari, C. Scheuba, K. Kaczirek, and B. Niederle Estimated Risk of Pheochromocytoma Recurrence After Adrenal-Sparing Surgery in Patients With Multiple Endocrine Neoplasia Type 2A Arch Surg, December 1, 2006; 141(12): 1199 - 1205. [Abstract] [Full Text] [PDF]

				A. Machens, M. Brauckhoff, H.-J. Holzhausen, P. N. Thanh, H. Lehnert, and H. Dralle Codon-Specific Development of Pheochromocytoma in Multiple Endocrine Neoplasia Type 2 J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3999 - 4003. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Igaz, P. Articles by Ésik, O. Search for Related Content PubMed Articles by Igaz, P. Articles by Ésik, O.