RB1 and gastrointestinal stromal tumor: For illustration, previous studies have identified that mutations that involve the RB1 gene are associated with high-risk tumors and aggressive clinical behavior and that activating mutations in the RAS and phosphatidylinositol 3-kinase pathways contribute to TKI resistance.166,167Figure 4 illustrates co-occurring genetic alterations in KIT-mutated GIST in the AACR Project GENIE database.