Premium
Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10
Author(s) -
FrankRaue 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,
Dvořáková Šárka,
Bendlova Bela,
Czetwertynska Małgorzata,
Skasko Elżbieta,
Barontini Marta,
Sanso Gabriela,
Vorländer Christian,
Maia Ana Luiza,
Patocs Attila,
Links Thera P.,
de Groot Jan Willem,
Kerstens Michiel N.,
Valk Gerlof D.,
Miehle Konstanze,
Musholt Thomas J.,
Biarnes Josefina,
Damjanovic Svetozar,
Muresan Mihaela,
Wüster Christian,
Fassnacht Martin,
Peczkowska Mariola,
Fauth Christine,
Golcher Henriette,
Walter Martin A.,
Pichl Josef,
Raue Friedhelm,
Eng Charis,
Neumann Hartmut P.H.
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21385
Subject(s) - penetrance , pheochromocytoma , multiple endocrine neoplasia , biology , exon , germline , multiple endocrine neoplasia type 2 , germline mutation , genetics , mutation , hyperparathyroidism , proto oncogene proteins c ret , cancer research , medicine , endocrinology , phenotype , gene , receptor , neurotrophic factors , glial cell line derived neurotrophic factor
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 31:1–8, 2010. © 2010 Wiley‐Liss, Inc.