title: NRAS codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma.
abstract: BACKGROUND
  Known factors related to distant metastases in follicular thyroid carcinoma (FTC) included age, primary tumor size, and invasiveness. Distant metastasis is a main cause of death in FTC patients. Several studies showed that the presence of RAS mutations is also associated with poor clinical outcomes. We analyzed RAS mutations in FTC with distant metastases, FTC without a distant metastasis, follicular adenoma (FA), and nodular hyperplasia (NH). Furthermore, we elucidated the relationship between RAS mutations and clinical outcomes in FTC patients.
  
  
  METHODS
  We selected patients who underwent a thyroidectomy for FTC with distant metastases (n=28), size matched FTC specimens without a distant metastasis (n=28), FA (n=17), and NH (n=12). NRAS, HRAS, and KRAS mutations were assessed using direct sequencing.
  
  
  RESULTS
  Among 85 patients, 39 patients (46%) had RAS mutations. The NRAS codon 61 mutation (n=21; 25%) was the most common point mutation. HRAS codon 61, KRAS codon 12/13, and KRAS codon 61 mutations were found in 7, 6, and 4 patients, respectively. A NRAS codon 12/13 mutation was found in only 1 patient, and a HRAS codon 12/13 mutation was not found. RAS mutations were significantly more common in the FTC than FA or NH groups. Especially, the NRAS codon 61 mutation was associated with distant metastasis in patients with FTC.
  
  
  CONCLUSIONS
  The presence of a RAS mutation, especially a NRAS codon 61 mutation, was significantly associated with the distant metastasis. The NRAS codon 61 mutation status might be a potential prognostic factor in FTC patients.
authors.affiliation: 1 Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Jang
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Song
authors.forename: So Young
authors.initials: SY
authors.lastname: Sim
authors.forename: Hyemi
authors.initials: H
authors.lastname: Kwon
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Choi
authors.forename: Min Ji
authors.initials: MJ
authors.lastname: Jeon
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Han
authors.forename: Won Gu
authors.initials: WG
authors.lastname: Kim
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.forename: Young Kee
authors.initials: YK
authors.lastname: Shong
authors.forename: Won Bae
authors.initials: WB
authors.lastname: Kim
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D003062:Codon; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D013965:Thyroidectomy; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins