RET codon 804 mutations in multiple endocrine neoplasia 2: genotype-phenotype correlations and implications in clinical management.
Multiple endocrine neoplasia type 2 (MEN 2) is a genetic syndrome caused by germline mutations in the RET proto-oncogene. These mutations cause changes in either the cysteine-rich extracellular domain or, less commonly, the non-cysteine intracellular domains of the RET protein. The genotype-phenotype correlations of classical cysteine RET mutations have been the subject of several comprehensive reviews. Less is known about the characteristics of the non-cysteine RET mutations. Studies of familial medullary thyroid cancer and MEN 2A kindreds carrying non-cysteine RET mutations have revealed a wide array of phenotypes, variable penetrance, and a diverse clinical course. The observed heterogeneity in disease expression has important diagnostic, therapeutic and prognostic implications. This review summarizes the genotypic and phenotypic characteristics of RET codon 804 mutation, a prototype for the less well-defined non-cysteine RET mutations associated with MEN 2.
Mukherjee
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Beaumont Cancer Genetics Program, Beaumont Cancer Institute, William Beaumont Hospital, Royal Oak, MI 48073, USA. Sudipto.Mukherjee@beaumont.edu
Zakalik
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D
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000032:analysis*; D003545:Cysteine / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000601:surgery / Q000628:therapy; D019683:Penetrance; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D011519:Proto-Oncogenes; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000601:surgery / Q000628:therapy; D055815:Young Adult
D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; D003545:Cysteine