title: BRAF(V599E) mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas.
abstract: Activating mutations of BRAF have been identified in a variety of human cancers, most notably melanomas and papillary thyroid carcinomas (PTCs). The aim of the present study was to disclose the role of BRAF mutations in thyroid carcinoma development. Seventy-two thyroid tumors, including 60 PTCs, six follicular adenomas, five follicular carcinomas, and one anaplastic carcinoma, were studied. BRAF mutation screening focused on exon 15 and exon 11 of the gene by single-stranded conformational polymorphism and sequence analysis. Search of RET/PTC expression was conducted with the RT-PCR technique. The molecular genetic study of the BRAF gene showed the presence of a missense thymine to adenine transversion at nucleotide 1796, resulting in the V599E substitution, in 24 of 60 PTCs (40%), none of six follicular adenomas, and none of five follicular carcinomas or one anaplastic carcinoma. Moreover, nine of 60 PTCs (15%) presented RET/PTC expression. A genetico-clinical association analysis showed a statistically significant correlation between BRAF mutation and development of PTCs of the classic papillary histotype (P = 0.038). On the contrary, no link could be detected between expression of BRAF(V599E) and age at diagnosis, gender, dimension, and local invasiveness of the primary cancer, presence of lymph node metastases, tumor stage, and multifocality of the disease. These data clearly confirm that BRAF(V599E) is the more common genetic alteration found to date in adult sporadic PTCs, that it is unique for this thyroid cancer histotype, and that it might drive the development of PTCs of the classic papillary subtype.
authors.affiliation: Dipartimento di Medicina Interna, Università di Perugia, Perugia. efisio@dimisem.med.unipg.it
authors.forename: Efisio
authors.initials: E
authors.lastname: Puxeddu
authors.forename: Sonia
authors.initials: S
authors.lastname: Moretti
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
authors.forename: Cristina
authors.initials: C
authors.lastname: Romei
authors.forename: Raffaela
authors.initials: R
authors.lastname: Pascucci
authors.forename: Marco
authors.initials: M
authors.lastname: Martinelli
authors.forename: Cecilia
authors.initials: C
authors.lastname: Marino
authors.forename: Nicola
authors.initials: N
authors.lastname: Avenia
authors.forename: Esther Diana
authors.initials: ED
authors.lastname: Rossi
authors.forename: Guido
authors.initials: G
authors.lastname: Fadda
authors.forename: Antonio
authors.initials: A
authors.lastname: Cavaliere
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ribacchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Falorni
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.forename: Furio
authors.initials: F
authors.lastname: Pacini
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Fausto
authors.initials: F
authors.lastname: Santeusanio
mesh_terms: D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D018698:Glutamic Acid / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D018698:Glutamic Acid; D011505:Protein-Tyrosine Kinases; C093573:ret-PTC fusion oncoproteins, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf; D014633:Valine