Rare Molecular Variants of Gastrointestinal Stromal Tumors (GISTs): Clinical Implications and Overview of Current Evidence.

Gastrointestinal stromal tumors are the most common sarcomas of the gastrointestinal tract. They are characterized by a distinct molecular profile, most frequently involving activating mutations in the KIT or PDGFRA genes, the identification of which has enabled the development of effective targeted therapies and has significantly improved patient outcomes. Despite significant therapeutic advances, treatment with tyrosine kinase inhibitors remains associated with the risk of primary or secondary resistance in a subset of patients. This phenomenon has highlighted the considerable biological heterogeneity of gastrointestinal stromal tumor, encompassing not only canonical mutational variants but also rare molecular alterations with distinct pathogenic mechanisms and clinical implications. Growing evidence suggests that detailed molecular characterization of gastrointestinal stromal tumors is of critical clinical importance, enabling improved risk stratification, optimization of treatment selection, and identification of patients requiring alternative therapeutic strategies. Therefore, comprehensive molecular diagnostics should be an integral part of the diagnostic and therapeutic approach to this heterogeneous group of tumors. The aim of this study is to provide an overview of current knowledge on rare molecular variants of gastrointestinal stromal tumors, as well as the available data on their clinical course and sensitivity to tyrosine kinase inhibitors and other therapeutic strategies.