title: High rate of BRAF and RET/PTC dual mutations associated with recurrent papillary thyroid carcinoma.
abstract: OBJECTIVE
  Papillary thyroid carcinoma (PTC), the most common thyroid malignancy, usually possesses BRAF mutation or rearranged in translation (RET)/PTC rearrangements. PTC usually possesses BRAF mutation or RET/PTC rearrangements. The mutation status of patients with recurrent PTC has never been characterized in a large population.
  
  
  METHODS
  Mutation status was determined in a cohort of 54 patients with recurrent PTC and analyzed for clinicopathologic relationships. BRAF and ras mutations were determined by PCR and sequencing of genomic DNA. RET/PTC rearrangements were analyzed by reverse transcription-PCR.
  
  
  RESULTS
  BRAF mutation in exon 15 (V600E) was found in 42/54 (77.8%) recurrent PTC patients. The RET/PTC rearrangements were detected in 9 of 54 (16.7%) patients. In addition, 5 of 54 (9.3%) recurrent PTC patients had both a BRAF mutation and a RET/PTC rearrangement. The prevalence of tumors with dual mutations found in the recurrent population far exceeds the frequency historically reported for patients with primary PTC. Patients with dual mutations were significantly older (80% older than 45 years) than patients with a BRAF mutation alone (38% older than 45 years).
  
  
  CONCLUSIONS
  Recurrent PTC is significantly associated with a predominant BRAF mutation. RET/PTC rearrangements, although commonly associated with primary PTCs in younger patients, are uncommonly found in recurrent PTC patients. In addition, the incidence of dual mutations was higher in patients with recurrent PTC than in those primary PTC, as reported by others.
authors.affiliation: Department of Head and Neck Surgery, Pathology, and Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ying C
authors.initials: YC
authors.lastname: Henderson
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Shellenberger
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Williams
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Fredrick
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Cieply
authors.forename: Gary L
authors.initials: GL
authors.lastname: Clayman
mesh_terms: D000328:Adult; D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012008:Recurrence; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D018631:ras Proteins / Q000235:genetics
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D018631:ras Proteins