The location of KIT and PDGFRA gene mutations in gastrointestinal stromal tumours is site and phenotype associated.

AIMS To assess the relation between KIT and PDGFRA mutations and the site of origin, histological phenotype, and pathomorphologically determined risk assessment in gastrointestinal stromal tumours (GISTs). METHODS A series of 83 clinicopathologically characterised GISTs from 79 patients was analysed for KIT and PDGFRA mutations by polymerase chain reaction amplification, single strand conformation polymorphism analysis, and direct DNA sequencing. RESULTS KIT or PDGFRA mutations were found in 57 and 11 GISTs, respectively. Most KIT mutations involved exon 11 (46 cases), followed by exon 9 (10 cases). The PDGFRA mutations mostly affected exon 18 (eight cases), followed by exon 12 (three cases). There was a significant association between KIT exon 9 mutations and an intestinal origin of GISTs, and between PDGFRA mutations and gastric origin of the tumours. In addition, the presence of PDGFRA mutations was significantly associated with epithelioid/mixed histology, as was the absence of identified receptor tyrosine kinase mutations. Vice versa, KIT exon 11 mutations were almost exclusively found in spindle cell GISTs. Furthermore, the presence of any KIT and PDGFRA mutations and the presence of KIT mutations alone were significantly associated with high risk/malignant GISTs. CONCLUSIONS The location of KIT and PDGFRA mutations in GISTs is associated with the site of origin and histological phenotype. Genotyping of GISTs may be a helpful additional parameter in determining the biological profile of these tumours.