内淋巴囊肿瘤分子遗传学研究进展

Advances in the molecular genetics of endolymphatic sac tumor

内淋巴囊肿瘤(ELST)较为罕见,主要与VHL基因突变相关,VHL基因主要通过依赖缺氧诱导因子途径引起VHL病。单独的VHL突变不足以导致肿瘤发生,VHL基因突变需要同样位于3号染色体短臂上的相关抑癌基因(PBRM1、SETD2、BAP1)的协同作用,才能最终导致肿瘤发生。散发性ELST中,第一外显子的突变最为常见,VHL病相关性ELST中,第三外显子的突变最为常见。ELST最常见的突变形式是截短突变。靶向治疗研究主要集中在血管内皮生长因子(VEGF)通路、缺氧诱导因子(HIF)通路、mTOR通路、促红细胞生成素(EPO)通路,抑制肿瘤生长和血管形成。全基因测序、单细胞测序等新技术的应用,也必将为更加全面地解释ELST的发病机制和治疗策略提供分子依据。

Endolymphatic sac tumor(ELST)is a rare neoplasm primarily associated with mutations in the VHL gene,which causes von Hippel-Lindau(VHL)disease through hypoxia-inducible factor-dependent pathways.While loss of the VHL gene is necessary for tumorigenesis,it alone is insufficient;additional tumor suppressor genes such as PBRM1,SETD2,BAP1 are also required.Sporadic ELST predominantly exhibited mutations in exon 1,whereas those related to VHL-disease showed more frequent mutations in exon 3.Truncating alterations represent the most common mutation observed in both types of ELST.Research into molecule-targeted therapies mainly focuses on inhibition tumor growth and angiogenesis via vascular endothelial growth factor(VEGF),hypoxia inducible factor(HIF),mTOR and erythropoietin(EPO)pathways.Emerging techniques such as whole genome sequencing and single-cell sequencing will provide further molecular evidence on the pathogenesis and potential treatment strategies for ELST.