Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10

Frank-Raue, Karin; Rybicki, Lisa A; Erlic, Zoran; Schweizer, Heiko; Winter, Aurelia; Milos, Ioana; Toledo, Sergio P A; Toledo, Rodrigo A; Tavares, Marcos R; Alevizaki, Maria; Mian, Caterina; Siggelkow, Heide; Hüfner, Michael; Wohllk, Nelson; Opocher, Giuseppe; Dvo?áková, Sárka; Bendlova, Bela; Czetwertynska, Ma?gorzata; Skasko, El?bieta; Barontini, Marta; ... (2011). Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10. Human mutation, 32(1), pp. 51-8. Hoboken, N.J.: Wiley-Blackwell 10.1002/humu.21385

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine
UniBE Contributor:	Walter, Martin Alexander
ISSN:	1059-7794
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:13
Last Modified:	05 Dec 2022 14:02
Publisher DOI:	10.1002/humu.21385
PubMed ID:	20979234
Web of Science ID:	000286281800014
URI:	https://boris.unibe.ch/id/eprint/2866 (FactScience: 205801)