title: Does the RET variant G691S influence the features of sporadic medullary thyroid carcinoma?
abstract: OBJECTIVE
  The RET (rearranged during transfection) proto-oncogene G691S variant is over-represented in the germline of patients with sporadic medullary thyroid carcinoma (sMTC) vs. normal controls but so far is not associated with any medical or pathological features of the tumour. The aim of our study was to assess the influence of this variant on the age of onset, clinical, biological and pathological features of sMTC.
  
  
  METHODS
  One hundred patients with histologically proven MTC, for whom the germline genetic analysis of RET was negative and medical records were available, were included in the study.
  
  
  RESULTS
  Patients with the heterozygous GS variant or the homozygous SS variant (n = 36) were on average 8.0 years younger than patients with the wild-type GG variant (n = 64, mean age 43.9 vs. 51.9 years, P < 0.01). The former group did not differ from the wild-type group in terms of MTC size, prevalence of C-cell hyperplasia (CCH) or papillary thyroid carcinoma (PTC). However, the prevalence of an increased preoperative basal calcitonin (bCT) level (> 1000 pg/ml) was 2.75-fold higher in the patients with the GS or SS variant than in those with the wild-type variant (P < 0.001). The proportion of patients with lymph node metastases was also higher in the former group (P < 0.05). Multivariate analysis confirmed that the presence of the RET variant is independently associated with higher preoperative bCT values (P = 0.011).
  
  
  CONCLUSIONS
  Our data demonstrate that the RET G691S variant could modulate the age of onset of sMTC as demonstrated previously for familial tumours. Moreover, this variant is an independent predictor of a higher basal calcitonin synthesis rate in patients with sMTC.
authors.affiliation: Service d'Endocrinologie et maladies métaboliques, Clinique Marc Linquette, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Cardot-Bauters
authors.forename: E
authors.initials: E
authors.lastname: Leteurtre
authors.forename: L
authors.initials: L
authors.lastname: Leclerc
authors.forename: M-C
authors.initials: MC
authors.lastname: Vantyghem
authors.forename: C
authors.initials: C
authors.lastname: Do Cao
authors.forename: J-L
authors.initials: JL
authors.lastname: Wemeau
authors.forename: M
authors.initials: M
authors.lastname: d'Herbomez
authors.forename: B
authors.initials: B
authors.lastname: Carnaille
authors.forename: V
authors.initials: V
authors.lastname: Barbu
authors.forename: S
authors.initials: S
authors.lastname: Pinson
authors.forename: P
authors.initials: P
authors.lastname: Pigny
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D018276:Carcinoma, Medullary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation / Q000502:physiology; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000502:physiology; D012189:Retrospective Studies; D012694:Serine / Q000235:genetics; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012694:Serine; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D005998:Glycine