title: The clinical spectrum of RET proto-oncogene mutations in codon 790.
abstract: OBJECTIVE
  Due to a strong genotype-phenotype correlation, the timing of prophylactic thyroidectomy in rearranged during transfection (RET) gene mutation carriers is usually dictated by genetic analysis.
  
  
  METHODS
  We report a nationwide retrospective study of the clinical data of 77 French patients from 19 families with a mutation in codon 790 of the RET proto-oncogene.
  
  
  RESULTS
  The average age at diagnosis was 35.6 years ± 20.5. Thirty-nine patients were women. Fifty-five patients underwent operations for the treatment of medullary thyroid carcinoma (MTC) at the mean age of 38 years (4-82 years). The mean follow-up duration was 89 months. TNM staging was as follows: T0NxMx in 19, TxNxMx in 1, T1NxMx in 22, T1N1Mx in 8, T2N1Mx in 1 and T3N1Mx in four patients. In the T1/x-Nx group, 96% were considered cured after surgery. In the N1 group (n=13), six patients had multifocal disease and five patients were cured. Age and gender were not significant predictors of remission. Twenty-two patients did not undergo an operation (age 1.5-78 years); among them, 11 patients had a mean basal calcitonin (CT) level of 9.8 pg/ml (2-24) after 53 months of follow-up. One patient had been operated on for phaeochromocytoma (PHEO), and their CT level remained normal for 262 months.
  
  
  CONCLUSIONS
  This study confirms that RET 790 mutation is associated with a non-aggressive form of multiple endocrine neoplasia type 2, as 28% of the patients were followed up without thyroidectomy, 25% had been thyroidectomised with no tumour being detected and even patients with MTC had slow-evolving disease. Moreover, only one patient had PHEO, and no-one had primary hyperparathyroidism.
authors.affiliation: Department of Endocrinology, Diabetes Mellitus and Metabolic Diseases, Avicenne Hospital, 125 route de Stalingrad, 93009 Bobigny Cedex, France. helene.bihan@avc.aphp.fr
authors.forename: Hélène
authors.initials: H
authors.lastname: Bihan
authors.forename: Arnaud
authors.initials: A
authors.lastname: Murat
authors.forename: Marinos
authors.initials: M
authors.lastname: Fysekidis
authors.forename: Abdallah
authors.initials: A
authors.lastname: Al-Salameh
authors.forename: Claire
authors.initials: C
authors.lastname: Schwartz
authors.forename: Eric
authors.initials: E
authors.lastname: Baudin
authors.forename: Philippe
authors.initials: P
authors.lastname: Thieblot
authors.forename: Françoise
authors.initials: F
authors.lastname: Borson-Chazot
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Guillausseau
authors.forename: Catherine
authors.initials: C
authors.lastname: Cardot-Bauters
authors.forename: Isabelle
authors.initials: I
authors.lastname: Raingeard
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Requeda
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Sadoul
authors.forename: Yves
authors.initials: Y
authors.lastname: Reznik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018278:Carcinoma, Neuroendocrine; D002648:Child; D002675:Child, Preschool; D003062:Codon; D005260:Female; D005602:France; D056726:Genetic Association Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D009154:Mutation; D009367:Neoplasm Staging; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D013961:Thyroid Gland / Q000473:pathology / Q000601:surgery; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy / Q000009:adverse effects; D055815:Young Adult
chemical_list: D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human