title: [Germline mutations of the ret proto-oncogene in Chilean patients with hereditary and sporadic medullary thyroid carcinoma].
abstract: BACKGROUND
  Medullary thyroid carcinoma (MTC) may occur either as a sporadic or familial disease. Multiple endocrine neoplasia (MEN) type 2, inherited as an autosomal dominant disease, is characterized by MTC only (FMTC) or coexistence of MTC with other endocrine neoplasia (NEM 2A, 2B). Germline mutations of the RET proto-oncogene (cRet) are found in the inherited forms and in some apparently sporadic MTC cases.
  
  
  OBJECTIVE
  To study RET mutations in 8 families with MEN 2.
  
  
  METHODS
  RET mutations were screened in peripheral blood DNA from 18 patients and 87 high risk carriers belonging to 8 MEN 2 families and 52 sporadic MTC. Exons 10, 11, 13, 14, 15 and 16 of the c-Ret were amplified by polymerase chain reaction (PCR) and examined by direct sequencing of PCR products and/or restriction enzyme analysis.
  
  
  RESULTS
  Five MEN 2A and one FMTC families with a germline mutation at codon 634, one MEN 2A and one FMTC family carrying a mutation at codon 620 were identified. Mutations were found in 23 out of 87 high risk carriers. In addition, we detected a S891A (exon 15) germline mutation in a sporadic MTC patient and in one out of her three sons and V804M (exon 14) in another sporadic MTC case and in one out of his six relatives, indicating in both cases the presence of a sporadic misclassified familial disease.
  
  
  CONCLUSIONS
  These results underscore the importance of routine application of c-Ret testing in all cases of MTC either familial or sporadic.
authors.affiliation: Sección de Endocrinología, Departamento de Medicina, Hospital del Salvador, Laboratorio IEMA, Santiago de Chile. iema@terra.cl
authors.forename: N
authors.initials: N
authors.lastname: Wohllk
authors.forename: P
authors.initials: P
authors.lastname: Becker
authors.forename: R
authors.initials: R
authors.lastname: Youlton
authors.forename: G J
authors.initials: GJ
authors.lastname: Cote
authors.forename: R F
authors.initials: RF
authors.lastname: Gagel
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002675:Child, Preschool; D002677:Chile; D029721:Drosophila Proteins; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000150:complications / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020539:Sequence Analysis, Protein; D013964:Thyroid Neoplasms / Q000150:complications / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila