Media type: E-Article Title: Genetic analysis of RET, GFRα1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A Contributor: Gil, Laura; Azañedo, Marta; Pollán, Marina; Cristobal, Eva; Arribas, Begoña; García‐Albert, Luis; García‐Sáiz, Alfredo; Maestro, María Luisa; Torres, Antonio; Menárguez, Javier; Rojas, José M. imprint: Wiley, 2002 Published in: International Journal of Cancer Language: English DOI: 10.1002/ijc.10298 ISSN: 1097-0215; 0020-7136 Keywords: Cancer Research ; Oncology Origination: Footnote: Description: <jats:title>Abstract</jats:title><jats:p>Multiple endocrine neoplasia type 2A (MEN 2A) is associated with specific germline missense mutations in the <jats:italic>RET</jats:italic> 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 <jats:italic>RET</jats:italic>, <jats:italic>GFRα1</jats:italic> and <jats:italic>GDNF</jats:italic> 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 <jats:italic>RET</jats:italic> and position +22 (intron 7) of <jats:italic>GFRα1</jats:italic>. Furthermore, we observed strong co‐segregation between 2 polymorphisms of <jats:italic>RET</jats:italic> [G691S (exon 11) and S904S (TCC‐TCG, exon 15) (100%, Fisher's exact test, <jats:italic>p</jats:italic>< 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, <jats:italic>p</jats:italic> = 0.007). These findings suggest that the G691S and S904S variants of <jats:italic>RET</jats:italic> may somehow play a role on the age of onset of MEN 2A. © 2002 Wiley‐Liss, Inc.</jats:p> Access State: Open Access