Ret proto-oncogen mutations in Argentinian MEN-2 patients.

SANSÓ G; DOMENÉ HM; MAYORGA L; PUSIOL E; GARCÍA RUDAZ C; PERINETTI HA; ROQUÉ M,; IORCANSKY S; BARONTINI M

Gubbio

Congreso; Seventh International Workshop on Multiple Endocrine Neoplasias.; 1999

Different RET proto-oncogen mutations have been described assodicated to MEN2 syndrome. The aim of the present study was to characterize these mutations in an Argentinian population by studying patients presenting clinical signs of MEN2 syndrome and to extent the study to their relatives in order to detect asymptomatic carriers. RET mutations were determined by PCR amplification of exons 10,11 and 16 followed by direct sequencing and digestion with restriction enzymes. In 14 MEN2A families (100 members, 15 indez cases, ages 28-60 years) the following mutations were detected: TGC-CGC in 8 families, TGC-TAC in 3 families, TGC-TTC in 2 families and TGC-TGG in 1 family. In 5 index cases pehocromocytoma and medullary thyroid carcinoma presented simultaneously. Pheo involvement was bilateral in 7 patients and malignanr in another 2. All 15 patients underwent total thyroidectomy with complete ganglionar resection. IN all of them, MTC with node mestatses was histopathologically diagnosed. Five families with MEN2B were studied. All 5 patients presented an ATG-ACG mutation. The patients showed characrteristic phenotype and presented MTC with lymph node metastases, one patient had also brain metastases. Bilateral Pheo was present in only one of these patients. One family with FMTC was also studied, the mutation detected was a TGC-CGC. In agreement with data from other countries the most frequent mutations in the Argentinian population of MEN2A patients were Cys634Arg (57%) and Cys634Tyr (21%). Also in agreement with other reports MEN2B patients showed the typical 918 codon mutation. The mutations found in the FMTC family is Cys634Arg, the most frequent mutation in the MEN2A population indicating mandatory biochemical screening of Pheo during follow-up of MTC in these patients.