title: BRAFV600E mutation in the pathogenesis of a large series of papillary thyroid carcinoma in Czech Republic.
abstract: BACKGROUND
  Activating point mutation of the BRAF gene, the most common genetic alteration reported in papillary thyroid carcinomas (PTC), has been associated with poor prognostic characteristics.
  
  
  OBJECTIVE
  Our objective was to determine the frequency of BRAFV600E mutation in PTC tumor tissues from the period 1960-2007 and to correlate it with clinicopathological parameters.
  
  
  METHODS
  DNAs were extracted from 242 PTCs, 23 sporadic medullary carcinomas, one anaplastic carcinoma and 6 poorly differentiated carcinomas. The presence of BRAFV600E mutation was determined using single strand conformation polymorphism method and verified by direct sequencing.
  
  
  RESULTS
  BRAFV600E mutation was detected in 81 of 242 PTCs (33.5%), in one of 6 poorly differentiated carcinomas (16.7%) and in anaplastic carcinoma. BRAFV600E mutation was much less frequent in the follicular variant compared to classical variant and mixed follicular- classical variant of PTCs (p=0.001). BRAFV600E mutation was significantly associated with presence of nodal metastasis (p=0.029), more advanced TNM stage (p=0.014) and recurrence of disease (p=0.008). The mutation correlated with a higher age at diagnosis (p=0.049) and with a greater tumor size (p=0.041). Multivariate analysis confirmed these findings. The prevalence of BRAFV600E mutation before 1986 was significantly lower than after it (p=0.008).
  
  
  CONCLUSIONS
  Our data suggest that BRAFV600E mutation is associated with high-risk clinicopathological characteristics of PTC and worse prognosis of patients. The frequency of the mutation significantly varied during the observed period but rather because of the different age distribution of patients in particular periods than as a consequence of Chernobyl accident.
authors.affiliation: Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic. vlassyk@seznam.cz
authors.forename: V
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authors.lastname: Sykorova
authors.forename: S
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authors.lastname: Dvorakova
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authors.lastname: Ryska
authors.forename: J
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authors.lastname: Vcelak
authors.forename: E
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authors.lastname: Vaclavikova
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authors.lastname: Laco
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authors.initials: D
authors.lastname: Kodetova
authors.forename: R
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authors.lastname: Kodet
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authors.lastname: Cibula
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authors.lastname: Hlobilkova
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authors.lastname: Astl
authors.forename: D
authors.initials: D
authors.lastname: Vesely
authors.forename: J
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authors.lastname: Betka
authors.forename: J
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authors.lastname: Hoch
authors.forename: S
authors.initials: S
authors.lastname: Smutny
authors.forename: J
authors.initials: J
authors.lastname: Cap
authors.forename: P
authors.initials: P
authors.lastname: Vlcek
authors.forename: Z
authors.initials: Z
authors.lastname: Novak
authors.forename: B
authors.initials: B
authors.lastname: Bendlova
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D047852:Chernobyl Nuclear Accident; D003062:Codon / Q000235:genetics; D018153:Czech Republic / Q000453:epidemiology; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D003062:Codon; D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf