title: Mutation analysis of the RET proto-oncogene and early thyroidectomy: results of a Portuguese cancer centre.
abstract: BACKGROUND
  Evidence that germline mutations in the RET proto-oncogene are the underlying cause of the familial form of medullary thyroid carcinoma (MTC) made it possible to identify gene carriers with a very high degree of accuracy. Aiming to define the mutational profile observed in our patients and to assess gene carriers' compliance with an early surgery, we reviewed results of molecular analysis of RET performed at our institution since 1994.
  
  
  METHODS
  One hundred fifty-eight individuals were screened for germline mutations of the RET proto-oncogene. Seventy-seven patients had apparently sporadic MTC; 8 patients had both MTC and pheochromocytoma or MTC and clinical features of multiple endocrine neoplasia type 2B despite a negative family history; 8 patients were known to belong to affected kindreds; and 65 individuals were at-risk individuals to develop MTC.
  
  
  RESULTS
  A germline mutation in RET was identified in 4% of apparently sporadic MTC patients, in 100% of patients with MTC and pheochromocytoma or MTC and clinical features of multiple endocrine neoplasia type 2B, and in 100% of probands of clinically established kindreds. The most affected codon was 634 (58%) followed by codon 804 (16%). Among at-risk individuals, 49% were identified as gene carriers. Seven individuals were submitted to prophylactic thyroidectomy (mean age, 17.7 +/- 12.5 years; range: 3-42 years), and all but 1 had MTC.
  
  
  CONCLUSIONS
  RET mutational spectrum observed in the present population disclosed a higher frequency of codon 804 mutations than expected. Compliance with an early prophylactic surgery seemed to be influenced not only by medical advice and cultural factors but also by the aggressiveness of disease in gene carriers' families.
authors.affiliation: Department of Endocrinology, Portuguese Cancer Center, Lisboa, Portugal. mjbugalho@ipolisboa.minsaude.pt
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Bugalho
authors.forename: Rita
authors.initials: R
authors.lastname: Domingues
authors.forename: Jorge Rosa
authors.initials: JR
authors.lastname: Santos
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Catarino
authors.forename: Luís
authors.initials: L
authors.lastname: Sobrinho
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D001483:Base Sequence; D002173:Cancer Care Facilities; D018276:Carcinoma, Medullary / Q000235:genetics / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics; D011174:Portugal; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D011519:Proto-Oncogenes; D013964:Thyroid Neoplasms / Q000235:genetics / Q000517:prevention & control; D013965:Thyroidectomy
chemical_list: D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human