title: Platelet-derived growth factor receptor family mutations in gastrointestinal stromal tumours.
abstract: OBJECTIVE
  Activating mutations of either KIT or platelet-derived growth factor receptor alpha (PDGFRA) genes are present in the majority of gastrointestinal stromal tumours (GISTs). The type of gene mutation is associated with the aggressiveness of the disease, response to imatinib therapy, and the tumour site in the gastrointestinal tract. However, a subgroup of GISTs does not harbour these mutations.
  
  
  METHODS
  Thirty-three GISTs were studied for mutations in exons encoding the juxtamembrane and the activation loop domains of KIT, PDGFRA, PDGFRB, CSF1R, and FLT3 genes using denaturing high-performance liquid chromatography and gene sequencing.
  
  
  RESULTS
  Twenty-two (67%) GISTs had mutation in KIT and 3 (9%) in PDGFRA. The three PDGFRA mutations were all detected in exon 18 of the gene. Three of the 5 GISTs that had weak to moderate KIT expression had a PDGFRA mutation as compared to none of the 26 cases with strong KIT immunopositivity (p=0.022). No mutations were found in PDGFRB, CSF1R or FLT3 in the 8 cases that did not harbour KIT or PDGFRA mutations.
  
  
  CONCLUSIONS
  KIT and PDGFRA are the most commonly mutated type III receptor tyrosine kinase genes in GIST. GISTs with PDGFRA mutations often have reduced expression of the KIT protein in immunohistochemistry, suggesting that immunohistochemistry may be potentially useful in identification of such GISTs.
authors.affiliation: Laboratory of Molecular Oncology, Biomedicum, Haartmaninkatu 8, PO Box 700, FIN-00029 Helsinki, Finland. harri.sihto@helsinki.fi
authors.forename: Harri
authors.initials: H
authors.lastname: Sihto
authors.forename: Kaarle
authors.initials: K
authors.lastname: Franssila
authors.forename: Minna
authors.initials: M
authors.lastname: Tanner
authors.forename: Carita
authors.initials: C
authors.lastname: Vasama-Nolvi
authors.forename: Maarit
authors.initials: M
authors.lastname: Sarlomo-Rikala
authors.forename: Nina N
authors.initials: NN
authors.lastname: Nupponen
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Jorma
authors.initials: J
authors.lastname: Isola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010534:Peritoneal Neoplasms / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor