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An overview on molecular biology of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumours (GIST)
  1. Margherita Nannini1,
  2. Guido Biasco1,2,
  3. Annalisa Astolfi2,
  4. Maria A Pantaleo1,2
  1. 1Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
  2. 2“Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, Italy
  1. Correspondence to Dr Margherita Nannini, Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; maggie.nannini{at}


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.

  • Gastrointestinal stromal tumours
  • KIT/PDGFRA wild-type
  • Succinate dehydrogenase
  • Insulin growth factor receptor 1
  • BRAF

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