title: BRAF, p53 and SOX2 in anaplastic thyroid carcinoma: evidence for multistep carcinogenesis.
abstract: OBJECTIVE
  The aim of this study was to genotype a series of papillary thyroid carcinomas (PTCs) and anaplastic thyroid carcinomas (ATCs) for BRAF mutation, and to evaluate p53 and SOX2 expression as factors implicated in tumour progression.
  
  
  METHODS
  The study included 17 PTCs and 14 ATCs. Analysis of the exon 15 of BRAF was based on direct sequencing. Immunohistochemistry was used to evaluate p53 and SOX2 expression.
  
  
  RESULTS
  V600E (c.1799T>A) mutation was observed in 53% (9/17) of PTCs. Two cases of ATCs (2/14; 14%), both with PTC component, harboured BRAF mutation: the classical V600E mutation and an undocumented duplication of codon 599 (c.1795_1797dup; p.Thr599dup). These mutations were present in ATC as well as PTC tumour cells. Overexpression of p53 and SOX2 was depicted respectively in 64% (9/14) and 29% (4/14) of ATCs, and absent in PTCs.
  
  
  CONCLUSIONS
  We confirm that V600E mutation is a frequent and specific event in PTC. BRAF-mutated ATCs are associated with a PTC component displaying the same mutation. We describe a new mutation of BRAF, T599dup, in a case of ATC with tall cell PTC component. Moreover, progression from PTC to ATC could be favoured by further TP53 mutation and SOX2 expression.
authors.affiliation: Department of Pathology, Hôpital Central, CHU, Nancy, France. g.gauchotte@yahoo.fr
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gauchotte
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippe
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lacomme
authors.forename: Brigitte
authors.initials: B
authors.lastname: Léotard
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Wissler
authors.forename: Lila
authors.initials: L
authors.lastname: Allou
authors.forename: Bruno
authors.initials: B
authors.lastname: Toussaint
authors.forename: Marc
authors.initials: M
authors.lastname: Klein
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vignaud
authors.forename: Aude
authors.initials: A
authors.lastname: Bressenot
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics* / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D016159:Tumor Suppressor Protein p53; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf