6533b86cfe1ef96bd12c8195
RESEARCH PRODUCT
Risk Profiles and Penetrance Estimations in Multiple Endocrine Neoplasia Type 2A Caused by Germline RET Mutations Located in Exon 10
K Frank RaueLa RybickiZ ErlicH SchweizerA WinterI MilosSp ToledoRa ToledoMr TavaresM AlevizakiCaterina MianH SiggelkowM HüfnerN WohllkOpocher Giuseppe DvoS ÁKováB BendlovaM CzetwertynskaE SkaskoM Barontini SansogC VorländerAl MaiaA PatocsTp Links De Groot JwMn KerstensGd ValkK MiehleTj MusholtJ BiarnesS DamjanovicM MuresanC WüsterM FassnachtM PeczkowskaC FauthH GolcherMa WalterJ PichlF RaueC EngHp Neumann For The International Ret Exon Consortiumsubject
MalePHEOCHROMOCYTOMAendocrine system diseasesMEDULLARY-THYROID CARCINOMAAdrenal Gland NeoplasmsMultiple Endocrine Neoplasia Type 2aPenetrancemedicine.disease_causePHENOTYPEGermlineExon0302 clinical medicinemedullary thyroid carcinomaMEN2BMEN2AChildGenetics (clinical)GeneticsAged 80 and overMutationHyperparathyroidismLife SciencesExonsMiddle AgedCARRIERSPenetranceCANCERPROPHYLACTIC THYROIDECTOMY3. Good healthgenotype-phenotypeFAMILYMEN2030220 oncology & carcinogenesisChild PreschoolFemaleAdultAdolescent030209 endocrinology & metabolismMultiple endocrine neoplasia type 2BiologyPheochromocytoma03 medical and health sciencesYoung AdultGermline mutationGeneticsmedicineHumansThyroid NeoplasmsCodonGerm-Line MutationAgedNeoplasm StagingProto-Oncogene Proteins c-retCancerHIRSCHSPRUNG-DISEASEPROTOONCOGENEmedicine.diseaseGENECarcinoma NeuroendocrineCancer researchRETdescription
Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609-620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected. Hum Mutat 32:51-58, 2011. (C) 2010 Wiley-Liss, Inc.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-11-16 | Human Mutation |