Utvrđivanje c-KIT mutacije na eksonima 9 i 11 u gastrointestinalnom stromalnom tumoru

master's thesis

• Title (english): Identification of c-KIT mutation on exons 9 and 11 in gastrointestinal stromal tumour
• Author: Ivana Gunjača
• Mentor: Irena Drmić-Hofman (mentor)
• Mentor: Maja Matulić (sumentor)
• Committee member: Nada Oršolić (predsjednik povjerenstva)
• Committee member: Gordana Lacković-Venturin (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2010, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

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.

Abstract (english)

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.

• Keywords: GIST; c-KIT; imatinib mezilat; lančana reakcija polimeraze; direktno sekvenciranje
• Keywords (english): GIST; c-KIT; imatinib mesilat; polymerase chain reaction; direct sequencing
• Language: croatian
• URN:NBN: urn:nbn:hr:217:053160
• Study programme: Title: Biology; specializations in: Molecular biology; Course: Molecular biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra biologije (magistar/magistra biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-23 11:41:43