Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy.
Int J Mol Sci. 2020 May 7;21(9):3313. doi: 10.3390/ijms21093313.
Gastrointestinal stromal tumors (GIST) are rare neoplasms of mesenchymal origin arising in the gastrointestinal tract. The vast majority are characterized by mutually exclusive activating mutations in KIT or Platelet-derived growth factor alpha (PDGFRA) receptors, or less frequently by succinate dehydrogenase complex (SDH) or NF1 inactivation, with very rare cases harboring mutant BRAF or RAS alleles. Approximately 5% of GISTs lack any of such mutations and are called wild-type (WT) GISTs. Recently, deregulated Fibroblast Growth Factor (FGF)/FGF-receptor (FGFR) signaling emerged as a relevant pathway driving oncogenic activity in different molecular subgroups of GISTs. This review summarizes all the current evidences supporting the key role of the FGF/FGFR pathway activation in GISTs, whereby either activating mutations, oncogenic gene fusions, or autocrine/paracrine signaling have been detected in WT, SDH-, or KIT-mutant GISTs.
胃肠道间质瘤（GIST）是一种罕见的起源于胃肠道的间叶源性肿瘤。绝大多数 GIST 具有相互排斥的 KIT 或血小板衍生生长因子受体α（PDGFRA）受体的激活突变，或不太常见的琥珀酸脱氢酶复合物（SDH）或 NF1 失活，极少数情况下存在突变 BRAF 或 RAS 等位基因。大约 5%的 GIST 缺乏任何此类突变，称为野生型（WT）GIST。最近，失调的成纤维细胞生长因子（FGF）/成纤维细胞生长因子受体（FGFR）信号转导被认为是驱动不同分子亚群 GIST 致癌活性的相关途径。这篇综述总结了所有支持 FGF/FGFR 通路激活在 GIST 中关键作用的现有证据，其中在 WT、SDH-或 KIT 突变型 GIST 中检测到了激活突变、致癌基因融合或自分泌/旁分泌信号。
