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Succinate dehydrogenase deficiency in pediatric and adult gastrointestinal stromal tumors.
- Source :
- Frontiers in Oncology; May2013, Vol. 3, p1-14, 14p
- Publication Year :
- 2013
-
Abstract
- Gastrointestinal stromal tumors (GISTs) in adults are generally driven by somatic gain-of-function mutations in KIT or PDGFRA, and biological therapies targeted to these receptor tyrosine kinases comprise part of the treatment regimen for metastatic and inoperable GISTs. A minority (10-15%) of GISTs in adults, along with ~85% of pediatric GISTs, lacks oncogenic mutations in KIT and PDGFRA. Not surprisingly these wild type (WT) GISTs respond poorly to kinase inhibitor therapy. A subset of WT GISTs shares a set of distinguishing clinical and pathological features, and a flurry of recent reports has convincingly demonstrated shared molecular characteristics. These GISTs have a distinct transcriptional profile including over-expression of the insulin-like growth factor-1 receptor, and exhibit deficiency in the succinate dehydrogenase (SDH) enzyme complex. The latter is often but not always linked to bi-allelic inactivation of SDH subunit genes, particularly SDHA. This review will summarize the molecular, pathological, and clinical connections that link this group of SDH-deficient neoplasms, and offer a view toward understanding the underlying biology of the disease and the therapeutic challenges implicit to this biology. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2234943X
- Volume :
- 3
- Database :
- Complementary Index
- Journal :
- Frontiers in Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 88067165
- Full Text :
- https://doi.org/10.3389/fonc.2013.00117