Gastrointestinal Stromal Tumors: The GIST of Precision Medicine

Trends Cancer. 2018 Jan;4(1):74-91. doi: 10.1016/j.trecan.2017.11.006. Epub 2017 Dec 23.


The discovery of activated KIT mutations in gastrointestinal (GI) stromal tumors (GISTs) in 1998 triggered a sea change in our understanding of these tumors and has ushered in a new paradigm for the use of molecular genetic diagnostics to guide targeted therapies. KIT and PDGFRA mutations account for 85-90% of GISTs; subsequent genetic studies have led to the identification of mutation/epimutation of additional genes, including the succinate dehydrogenase (SDH) subunit A, B, C, and D genes. This review focuses on integrating findings from clinicopathologic, genetic, and epigenetic studies, which classify GISTs into two distinct clusters: an SDH-competent group and an SDH-deficient group. This development is important since it revolutionizes our current management of affected patients and their relatives, fundamentally, based on the GIST genotype.

Keywords: BRAF; Carney triad; Carney–Stratakis syndrome; GIST; KIT; KRAS; NF-1; PDGFRA; SDH; SDHCme; gastrointestinal stromal tumor; imatinib.

Publication types

  • Review

MeSH terms

  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology
  • Germ-Line Mutation
  • Humans
  • Mutation
  • Precision Medicine
  • Proto-Oncogene Proteins c-kit / genetics*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Succinate Dehydrogenase / genetics*


  • Succinate Dehydrogenase
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha