Molecular genetics

Abstract

Numerous advances were made in thelast decade in the research of gastrointestinal stromal tumors (GIST). The success in GIST diagnosis, therapy and prognosis was associated with discovery of mutations in the genes of two receptor tyrosine kinases, namely c-kit receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor A (PDGFRA). Identified mutations were found to be the oncogenic drivers for GIST development and progression. A new and very promising therapeutic agent, imatinib mesylate, with a strong and specific inhibitory action on relevant receptor tyrosine kinases aberrant signaling, necessitated subsequent pilot therapies and clinical trials as a treatment for GIST. Unprecedented positive therapeutic responses were subsequently recorded and the successful targeted therapy story continued. It is now well known that mutations in the most relevant driver genes and recently identified genetic signatures play important roles in GIST diagnosis, staging, therapy, management and prognosis. Molecular analysis has become an inseparable part of the current personalized approach to clinical management of GIST patients.