New issues in gastrointestinal stromal tumors of the stomach

Gastrointestinal stromal tumors (GISTs) constitute the majority of mesenchymal tumors of the gastrointestinal tract. The activating mutations in the receptor tyrosine kinases KIT and PDFRA are key molecular changes in the pathogenesis of these tumors and their recognition has led to the development of targeted therapies. Approximately 10% of GISTs, referred to as wild-type, lack such mutations and respond poorly to treatment with tyrosine kinase inhibitors. These GISTs are almost exclusive to the stomach and include primarily tumors that occur in children and tumors that are part of several tumor syndromes. Recent studies have shown that most wild-type GISTs are succinate dehydrogenase deficient. This review summarizes current advances in the molecular biology of GISTs and discusses the clinical and pathologic features associated with different genotypes.