title: Difference in development of medullary thyroid carcinoma among carriers of RET mutations in codons 790 and 791.
abstract: OBJECTIVE
  Hereditary medullary thyroid carcinoma (MTC) is caused by germ-line mutations in the RET proto-oncogene. Our study addresses the difference in development of MTC between rare mutations in RET codons 790, 791 and 804.
  
  
  METHODS
  We evaluated tumour stage, calcitonin levels, biochemical cure rates and associated endocrinopathies in 153 German/Austrian patients with RET 790 (n = 47), 791 (n = 56) and 804 mutations (n = 50), divided into index- and screening groups.
  
  
  RESULTS
  Age at diagnosis in index-patients did not differ significantly among the three codon groups (medians of 57, 61 and 53 years). Tumour stage at diagnosis was significantly less advanced with codon 791 (n = 22) than 790 (n = 16) and 804 (n = 16) mutations (P = 0.001). In screening patients, age at diagnosis did not differ significantly among the three groups (medians 19, 24 and 32 years). Tumour stage at diagnosis was also significantly less advanced with codon 791 (n = 34) than 790 (n = 31) and 804 (n = 34) (P = 0.032). Preoperative basal calcitonin levels were significantly lower in codon 791 carriers compared to codon 790 carriers, and cure rates were significantly higher in both index (75%vs. 31%; P = 0.03) and screening patients (100%vs. 75%; P = 0.015). Additional endocrinopathies were observed only with codon 791 carriers (four pheochromocytomas and two hyperparathyroidism).
  
  
  CONCLUSIONS
  There is a significant difference in MTC development with less extensive C-cell disease, higher cure rate and more frequent additional endocrinopathies in carriers of RET codon 791 mutations compared with carriers of codons 790 and 804 mutations. This information should be considered when age of prophylactic thyroidectomy is discussed.
authors.affiliation: Endocrine Practice, Molecular Laboratory, Heidelberg, Germany. karin.frankraue@raue-endokrinologie.de
authors.forename: Karin
authors.initials: K
authors.lastname: Frank-Raue
authors.forename: Andreas
authors.initials: A
authors.lastname: Machens
authors.forename: Christian
authors.initials: C
authors.lastname: Scheuba
authors.forename: Bruno
authors.initials: B
authors.lastname: Niederle
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Raue
mesh_terms: D000328:Adult; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003062:Codon / Q000235:genetics; D005190:Family; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult
chemical_list: D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human