title: Genetic mutations in the treatment of anaplastic thyroid cancer: a systematic review.
abstract: BACKGROUND
  Anaplastic thyroid cancer (ATC) is a rare, lethal disease associated with a median survival of 6 months despite the best multidisciplinary care. Surgical resection is not curative in ATC patients, being often a palliative procedure. Multidisciplinary care may include surgery, loco-regional radiotherapy, and systemic therapy. Besides conventional chemotherapy, multi kinase-targeted inhibitors are emerging as novel therapeutic tools. The numerous molecular alteration detected in ATC are targets for these inhibitors. The aim of this review is to determine the prevalence of the major genetic alterations occurring in ATC and place the results in the context of the emerging kinase-targeted therapies.
  
  
  METHODS
  The study is based on published PubMed studies addressing the prevalence of BRAF, RAS, PTEN, PI3KCA and TP53 mutations and RET rearrangements in ATC.
  
  
  RESULTS
  21 articles dealing with 652 genetic analyses of the selected genes were used. The overall prevalence determined were the following: RET/PTC, 4%; BRAF, 23%; RAS, 60%; PTEN, 16%; PI3KCA, 24%; TP53, 48%. Genetic alterations are sometimes overlapping.
  
  
  CONCLUSIONS
  Mutations of BRAF, PTEN and PI3KCA genes are common in ATC, with RAS and TP53 being the most frequent. Given ATC genetic complexity, effective therapies may benefit from individualized therapeutic regimens in a multidisciplinary approach.
authors.forename: Anna
authors.initials: A
authors.lastname: Guerra
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Crescenzo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Garzi
authors.forename: Mariapia
authors.initials: M
authors.lastname: Cinelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Carlomagno
authors.forename: Massimo
authors.initials: M
authors.lastname: Tonacchera
authors.forename: Pio
authors.initials: P
authors.lastname: Zeppa
authors.forename: Mario
authors.initials: M
authors.lastname: Vitale
mesh_terms: D006801:Humans; D009154:Mutation; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000235:genetics*