Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The majority are sporadic, solitary tumors that harbor mutually exclusive KIT or PDGFRA gain-of-function mutations.1 The type of mutation in addition to risk stratification corresponds to the biological behavior of GIST and response to treatment.

Up to 85% of pediatric GISTs and 10-15% of adult GISTs are devoid of these (KIT/PDGFRA) mutations and are referred to as (wt-GIST)“Wild-type" gastrointestinal stromal tumors and are characterized by the lack of KIT and PDGFRA mutations, Although the pathogenesis is largely unknown, It has been shown that these wt-GISTs are a heterogeneous tumor group with regard to their clinical behavior and molecular profile. Recent advances in molecular pathology helped to further sub-classify the so-called "wt-GISTs". Based on their significant clinical and molecular heterogeneity, wt-GISTs are divided into a syndromic and a non-syndromic (sporadic) subgroup. recent studies have uncovered germline mutations ..... [to be continued].