Classification of KIT/PDGFRA wild-type gastrointestinal stromal tumors: implications for therapy. Issue 6 (June 2015)

• Record Type: Journal Article
• Authors: Huss, Sebastian; Elges, Sandra; Trautmann, Marcel; Sperveslage, Jan; Hartmann, Wolfgang; Wardelmann, Eva
• Is Part Of: Expert review of anticancer therapy. Volume 15:Issue 6(2015)
• Page Start: 623
• Page End: 628
• Publication Date: 2015-06
• Subjects: Cancer -- Treatment -- Periodicals; 616.99406
• DOI: 10.1586/14737140.2015.1032941
• Languages: English
• ISSNs: 1473-7140

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>Gastrointestinal stromal tumors (GIST) are driven mostly by oncogenic <italic>KIT</italic> or <italic>PDGFRA</italic> mutations. However, in 10–15% of all GIST, no such activating mutations can be found and these tumors are classified as 'wild-type GIST' (<italic>KIT/PDGFRA</italic> wt-GIST). Subgroups of <italic>KIT/PDGFRA</italic> wt-GIST are driven by other sporadic mutations involving the RAS/RAF/MAP-kinase pathway, such as BRAF or KRAS mutations. Furthermore, <italic>KIT/PDGFRA</italic> wt-GIST are observed in the context of hereditary syndromes, such as neurofibromatosis Type 1, in which the lack of neurofibromin 1 also leads to the activation of the RAS/RAF/MAP-kinase pathway. Finally, the deficiency succinate dehydrogenase seems to play a major role in <italic>KIT/PDGFRA</italic> wt-GIST. In conclusion, <italic>KIT/PDGFRA</italic> wt-GIST belong to different subgroups defined by diverse underlying genetic alterations leading to different biological phenotypes. The vast majority of <italic>KIT/PDGFRA</italic> wt-GIST will not respond to imatinib. Further research to unravel the pathogenesis of <italic>KIT/PDGFRA</italic> wt-GIST is prerequisite to the development of effective treatment strategies.</p> </abstract>