Gastrointestinal Stromal Tumors: Key to Diagnosis and Choice of Therapy

• Published in: Molecular diagnosis & therapy 2008-01, Vol.12 (3), p.131-143
• Main Authors: Rutkowski, Piotr, Debiec-Rychter, Maria, Ruka, Wlodzimierz
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cytogenetic Analysis; Disease Progression; Gastrointestinal Stromal Tumors - diagnosis; Gastrointestinal Stromal Tumors - genetics; Gastrointestinal Stromal Tumors - pathology; Gastrointestinal Stromal Tumors - therapy; Human Genetics; Humans; Laboratory Medicine; Molecular Diagnostic Techniques; Molecular Medicine; Pharmacotherapy
• ISSN: 1177-1062; 1179-2000
• DOI: 10.1007/BF03256278

The common feature of gastrointestinal stromal tumors (GISTs) is the expression of KIT protein or acquisition of activating, constitutive mutations in the KIT or platelet-derived growth factor receptor α ( PDGFRA ) genes that are the early oncogenic events during GIST development. With these discoveries, GIST has emerged as a distinct sarcoma entity, enabling the introduction of targeted therapy using the inhibition of KIT/PDGFRA and their downstream signaling cascade. The introduction of a small-molecule tyrosine kinase inhibitor, imatinib mesylate, to clinical practice has revolutionized the treatment of patients with advanced GISTs and is currently approved as first-line treatment for patients with metastatic and/or inoperable GISTs. Mutation screening is currently a tool in GIST diagnosis, assessment of sensitivity to tyrosine kinase inhibitors, and prediction of achieving response to molecularly targeted therapy. This article discusses the histologic and molecular criteria for distinguishing GISTs from other types of sarcoma, and the molecular diagnostic tools that are currently available or in development to assist in therapy decisions.