The characterization of c-Kit mutations in gastrointestinal stromal tumours

Abstract

Gastrointestinal stromal tumours (GISTs) are specifically mesenchymal tumours arising throughout the gastrointestinal tract. The incidence is of approximately 2/100,000, with a 5-year survival in 50% of the patients. Up to 80% of GISTs are CD117 positive due to a mutation in the c-Kit, whilst Platelet Derived Growth Factor Receptor Alpha (PDGFRA) mutation is mostlycharacterized by CD117 negativity. Surgery is the main treatment in cases of benign and located GISTs, and imatinib mesylate is used in cases of metastasis or non-operable cases. The c-Kit mutations which respond to imatinib therapy are found in exons 11 and 9 whilst those resistant are found in exons 13 and 17. Considering the recent immunohistochemical discoveries and the increase in identification involving diagnosis and clinical approach in GIST, the aim of this retrospective study is to assess the sensitivity of various molecular techniques used to identify mutations in KIT hotspot exons 11, 9, 13 and 17 by using DNA and RNA isolated from formalin-fixed-paraffin-embedded (FFPE) tumour material from GIST patients. The main objective is to identify the genetic mutational profiles of c-Kit in GIST patients. The mutational state will also provide a molecular classification of patients and give information on prediction of therapy outcome that can be introduced in the diagnostic service.