BRAF mutation in thyroid cancer

Endocr Relat Cancer. 2005 Jun;12(2):245-62. doi: 10.1677/erc.1.0978.

Abstract

Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF). Since the initial report of this mutation in thyroid cancer 2 years ago, rapid advancements have been made. BRAF mutation is the most common genetic alteration in thyroid cancer, occurring in about 45% of sporadic papillary thyroid cancers (PTCs), particularly in the relatively aggressive subtypes, such as the tall-cell PTC. This mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role, as demonstrated by transgenic mouse studies that showed BRAF mutation-initiated development of PTC and its transition to anaplastic thyroid cancer. BRAF mutation is mutually exclusive with RET/PTC rearrangement, and also displays a reciprocal age association with this common genetic alteration in thyroid cancer. The T1799A BRAF mutation occurs exclusively in PTC and PTC-derived anaplastic thyroid cancer and is a specific diagnostic marker for this cancer when identified in cytological and histological specimens. This mutation is associated with a poorer clinicopathological outcome and is a novel independent molecular prognostic marker in the risk evaluation of thyroid cancer. Moreover, preclinical and clinical evaluations of the therapeutic value of novel specific mitogen-activated protein kinase pathway inhibitors in thyroid cancer are anticipated. This newly discovered BRAF mutation may prove to have an important impact on thyroid cancer in the clinic.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Gene Rearrangement
  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mutation
  • Oncogene Proteins / genetics
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics*

Substances

  • Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Mitogen-Activated Protein Kinases