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Genetic analysis of RET, GFRα1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A
Author(s) -
Gil Laura,
Azañedo Marta,
Pollán Marina,
Cristobal Eva,
Arribas Begoña,
GarcíaAlbert Luis,
GarcíaSáiz Alfredo,
Maestro María Luisa,
Torres Antonio,
Menárguez Javier,
Rojas José M.
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10298
Subject(s) - glial cell line derived neurotrophic factor , proto oncogene proteins c ret , multiple endocrine neoplasia type 2 , exon , germline , missense mutation , biology , locus (genetics) , multiple endocrine neoplasia , exact test , germline mutation , genetics , intron , phenotype , gene , mutation , endocrinology , medicine , receptor , neurotrophic factors
Abstract Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germline missense mutations in the RET proto‐oncogene. This locus encodes a receptor tyrosine kinase whose activation requires the formation of a multimeric receptor complex including GDNF as a ligand and GFRα1 as a coreceptor. In order to explore the role of RET , GFRα1 and GDNF genes in the variation of phenotypes observed in MEN2A families, we analysed germline mutations of these genes in 4 unrelated Spanish MEN2A families (23 cases studied). We found 2 novel variants corresponding to a single change in position + 47 (intron 12) of RET and position +22 (intron 7) of GFRα1 . Furthermore, we observed strong co‐segregation between 2 polymorphisms of RET [G691S (exon 11) and S904S (TCC‐TCG, exon 15) (100%, Fisher's exact test, p < 0.001)]. More interestingly, we found that these polymorphisms occurred at a significantly high frequency in patients with age at onset < 20 years old (Kruskal‐Wallis's and Fisher's exact test, p = 0.007). These findings suggest that the G691S and S904S variants of RET may somehow play a role on the age of onset of MEN 2A. © 2002 Wiley‐Liss, Inc.