Identification of c-KIT mutation on exons 9 and 11 in gastrointestinal stromal tumour

Abstract

Gastrointestinalni stromalni tumori (GIST) su najčešći primarni mezenhimalni tumori gastrointestinalnog trakta, a karakterizira ih prekomjerna ekspresija i mutacije c-KIT receptora tirozin kinaze. Somatske mutacije koje su rezultat konstitutivne aktivacije KIT kinaze su utvrđene u brojnim kliničkim studijima GIST-a, iako se mutacije pojavljuju različitom učestalošću. U nekoliko izvještaja je potvrđeno da su mutacije gena KIT najizraženije kod malignih GIST-a nego u benignim lezijama, posebice u eksonima 9 i 11, za koje je dokazano da imaju negativni prognostički faktor. U ovom su radu analizirane mutacije direktnim sekvenciranjem umnoženih dijelova DNA eksona 9 i 11 u 12 uzoraka GIST-a. Analizom uzoraka tkiva uklopljenog u parafin od 12 bolesnika s operiranim GIST-om pronađeno ih je devet (75%) s missense mutacijama odnosno nukleotidnim supstitucijama u eksonu 11, jedan s mutacijom delecije baza, isto u eksonu 11, a u eksonu 9 je u jednom uzorku uz missense mutaciju pronađena i insercijska mutacija.Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal tumours of the gastrointestinal tract and are characterized by overexpression and mutation of c-KIT, receptor tyrosine kinase. Somatic mutations that result in constitutive activation of KIT kinase have been identified in a number of clinical studies of GISTs, although the reported frequency of these mutations has varied over a wide range. Several reports have suggested that KIT gene mutations are more common in malignant GISTs than in benign lesions, and it has been proposed that mutations in exon 9 and exon 11 of KIT are negative prognostic factor. In this study mutations were characterised by direct DNA sequencing for screening polymerase chain reaction amplimers of exons 9 and 11 from GIST genomic DNA. Missense mutations within the exon 11 have been identified in nine (75%) of twelve patients, one patient had a deletion in exon 11 and one patient had a insertion within exon 9 of KIT