title: Genetic Alterations in Differentiated Thyroid Cancer Patients with Acromegaly.
abstract: OBJECTIVE
  Acromegaly is associated with increased thyroid cancer risk. We aimed to analyze the frequency of point mutations of BRAF and RAS genes, and RET/PTC, PAX8/PPARγ gene rearrangements in patients with acromegaly having differentiated thyroid cancers (DTC) and their relation with clinical and histological features.
  
  
  METHODS
  14 acromegalic patients (8 male, 6 female) with DTC were included. BRAF V600E and NRAS codon 61 point mutations, RET/PTC1, RET/PTC3, and PAX8/PPARγ gene rearrangements were analyzed in thyroidectomy specimens. We selected 14 non-acromegalic patients with DTC as a control group.
  
  
  RESULTS
  2 patients (14.3%) were detected to have positive BRAF V600E and 3 patients (21.4%) were detected to have NRAS codon 61 mutation. NRAS codon 61 was the most frequent genetic alteration. Patients with positive mutation had aggressive histologic features more frequently than patients without mutations. Comparison of the acromegalic and non-acromegalic patients with DTC revealed that BRAF V600E mutation was more frequent in non-acromegalic patients with DTC (14.2% vs. 64.3%, p=0.02). RET/PTC 1/ 3, PAX8/PPARγ gene rearrangements were not detected in any patient. None of the patients including the patients with positive point mutations had recurrence, and local and/or distant metastasis.
  
  
  CONCLUSIONS
  NRAS codon 61 is the most frequent genetic alteration in this acromegaly series with DTC. Since acromegalic patients have lower prevalance of BRAF V600E mutation, BRAF V600E mutation may not be a causative factor in development of DTC in acromegaly. Despite the relation of BRAF V600E and NRAS codon 61 mutations with aggresive histopathologic features, their impact on tumor prognosis remains to be defined in acromegaly in further studies.
authors.affiliation: Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Aydin
authors.affiliation: Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: C
authors.initials: C
authors.lastname: Aydin
authors.affiliation: Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Dagdelen
authors.affiliation: Department of Pathology, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: G G
authors.initials: GG
authors.lastname: Tezel
authors.affiliation: Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: T
authors.initials: T
authors.lastname: Erbas
mesh_terms: D000172:Acromegaly / Q000235:genetics*; D000328:Adult; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human