BRAF mutations in papillary carcinomas of the thyroid

Oncogene. 2003 Sep 25;22(41):6455-7. doi: 10.1038/sj.onc.1206739.


BRAF is a serine/threonine kinase that receives a mitogenic signal from RAS and transmits it to the MAP kinase pathway. Recent studies have reported that mutations of the BRAF gene were detected with varying frequencies in several cancers, notably more than 60% in melanoma. We analysed mutations of BRAF and RAS genes in 100 cases of thyroid carcinoma to investigate genetic aberrations in the RAS/RAF/MEK/MAP kinase pathway. BRAF mutations were detected exclusively in papillary carcinomas (40 in 76 cases: 53%), and were exclusively V599E, a mutation frequently observed in other carcinomas. NRAS mutation was observed in six cases (6%), all in histological types other than papillary carcinoma, and was exclusively Q61R. No mutations were found in KRAS or HRAS. Our results suggest that BRAF mutations may play a critical role in the carcinogenesis of papillary carcinoma of the thyroid.

MeSH terms

  • Carcinoma, Papillary / genetics*
  • Humans
  • Mutation*
  • Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf
  • Thyroid Neoplasms / genetics*
  • Thyrotropin / metabolism
  • ras Proteins / genetics


  • Oncogene Proteins
  • Thyrotropin
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • ras Proteins