Department of Hematology & Oncological Sciences L&A Seràgnoli, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy.
Future Oncol. 2013 Jan;9(1):121-6. doi: 10.2217/fon.12.170.
KIT/PDGF receptor-α (PDGFRA) wild-type (WT) gastrointestinal stromal tumors (GIST) are characterized by an overexpression of IGF-1 receptor (IGF1R) at the mRNA and protein level. More recently, germline and somatic mutations in succinate dehydrogenase (SDH) subunits A, B and C have been identified in KIT/PDGFRA WT sporadic GIST. Until now, the molecular basis of IGF1R overexpression in KIT/PDGFRA WT GIST has not been explained. In this brief report we investigate the status of the SDH complex at the genomic and protein level in relation to IGF1R expression at the mRNA and protein level in seven KIT/PDGFRA WT sporadic GIST patients. We found that IGF1R was upregulated in all patients harboring SDH mutations or displaying a SDH dysfunction, with respect to KIT/PDGFRA WT GIST without SDH mutations. Western blot analysis confirmed that all patients with an upregulation of IGF1R mRNA had detectable IGF1R protein expression. This report would suggest that IGF1R overexpression in KIT/PDGFRA WT GIST could be driven by the loss-of-function of the SDH mitochondrial complex.
KIT/PDGF 受体-α（PDGFRA）野生型（WT）胃肠道间质瘤（GIST）的特征是 IGF-1 受体（IGF1R）在 mRNA 和蛋白水平上的过度表达。最近，在 KIT/PDGFRA WT 散发性 GIST 中已经鉴定出琥珀酸脱氢酶（SDH）亚基 A、B 和 C 的种系和体细胞突变。到目前为止，KIT/PDGFRA WT GIST 中 IGF1R 过度表达的分子基础尚未得到解释。在本简要报告中，我们研究了 7 例 KIT/PDGFRA WT 散发性 GIST 患者中 IGF1R 表达的 mRNA 和蛋白水平与 SDH 复合物在基因组和蛋白水平上的状态。我们发现，在所有携带 SDH 突变或显示 SDH 功能障碍的患者中，IGF1R 均上调，而 KIT/PDGFRA WT GIST 中则没有 SDH 突变。Western blot 分析证实，所有 IGF1R mRNA 上调的患者均有可检测到的 IGF1R 蛋白表达。本报告提示，KIT/PDGFRA WT GIST 中 IGF1R 的过度表达可能是由 SDH 线粒体复合物的功能丧失驱动的。
