An overview on molecular biology of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumours (GIST)

J Med Genet. 2013 Oct;50(10):653-61. doi: 10.1136/jmedgenet-2013-101695. Epub 2013 Jul 5.


Background: About 85% of paediatric gastrointestinal stromal tumours (GISTs) and about 10-15% of adult GISTs do not harbour any mutations in the KIT and PDGFRA genes and are defined as KIT/PDGFRA wild type (WT). Over the years it has been demonstrated that KIT/PDGFRA WT GISTs are profoundly different from mutant GIST in clinical and molecular profiles, so that they are now considered a separate pathological entity. Moreover, due to their extreme molecular and clinical heterogeneity, KIT/PDGFRA WT GIST should be considered as a family of diseases and not as a single disease entity. However, although several genetic alterations belonging only to KIT/PDGFRA WT GIST have been identified, the exact role of these molecules in the pathogenesis and development of this subgroup is not yet defined.

Methods: The aim of this review is to report all current data about the molecular biology of syndromic and non-syndromic KIT/PDGFRA WT GIST, focusing on the potential clinical implication of each biological feature shared by this subgroup and discussing unresolved problems and future research perspectives on this topic.

Results: WT GIST is definitely a set of different diseases sustained by specific molecular alterations not yet completely known.

Conclusion: Large series of patients are required for defining the biological fingerprint of each subtype and integrating it with clinical data. This will allow the transfer of biological information to clinical practice and its use as an additional tool for diagnosis, prognosis and selection of medical treatment.

Keywords: BRAF; Gastrointestinal stromal tumours; Insulin growth factor receptor 1; KIT/PDGFRA wild-type; Succinate dehydrogenase.

Publication types

  • Review

MeSH terms

  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Proto-Oncogene Proteins c-kit / genetics*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Syndrome


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