SDHx基因突变引起的嗜铬细胞瘤/副神经节瘤研究进展  

The research progress of pheochromocytoma/paraganglioma caused by SDHx mutation

作　　者：申婉晴 史新冲[1] 张冰[1] 何巧[1] 张祥松[1] Shen Wanqing;Shi Xinchong;Zhang Bing;He Qiao;Zhang Xiangsong(Department of Nuclear Medicine,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第一医院核医学科,广州510080

出　　处：《国际遗传学杂志》2021年第5期346-352,共7页International Journal of Genetics

摘　　要：嗜铬细胞瘤/副神经节瘤(pheochromocytomes and paragangliomas,PCC/PGL)是分别产生于肾上腺髓质的嗜铬细胞和自主性副神经节的、少见的神经内分泌腺肿瘤,部分PCC/PGL由基因的突变引起。PCC/PGL具有广泛的遗传异质性,有20多个易感基因的突变可引起PCC/PGL。易感基因可分为两类,第一类基因,如SDHx(succinate dehydrogenase,SDH)、VHL、PHD2、FH、IDH、HIF2A和MDH2通过"伪缺氧"信号转导通路使嗜铬细胞发生转化,第二类基因,如RET、NF1、KIF1Bβ、MAX和TMEM127等,则通过激酶信号转导通路使嗜铬细胞发生转化。本文综述了SDHx(包括SDHD、SDHC、SDHB、SDHA、SDHAF1和SDHAF2基因)引起的PCC/PGL的基因型与临床表现型的关系、遗传异质性以及其在临床应用方面的研究进展,并对目前尚未完全揭晓的PCC/PGL发病的分子机制进行了简单的介绍,以期对研究PCC/PGL的发病机制、传递规律及其诊断、病情恶化风险评估和发现潜在的治疗手段有所启示,也可以为临床遗传咨询的改进提供理论参考。Pheochromocytomas and paragangliomas(PCC/PGL)are rare neuroendocrine tumors arising from the chromaffin cells of adrenal medulla and the neuroendocrine glands of autonomic paraganglion.These tumors can be of sporadic or hereditary origin,mutations in more than twenty susceptibility genes have implicated in the development of PCC/PGL,the disease-causing genes of PCC/PGL are mainly classified into two major groups.Cluster 1 genes are involved with the pseudo-hypoxic pathway and consisted of SDHx,VHL,PHD2,FH,IDH,HIF2A and MDH2.Cluster 2 genes are associated with abnormal activation of kinase signalling pathways and include RET,NF1,KIF1Bβ,MAX and TMEM127.This review addresses the research progress of the genotype-phenotype relationship for these hereditary syndromes caused by mutations of SDHx in cluster 1 genes,with an emphasis on the genetic heterogeneities of SDHx(SDHD,SDHC,SDHB,SDHA,SDHAF1 and SDHAF2),including the ongoing studies to uncover the molecular basis of tumorigenesis of PCC/PGL.The molecular research on pathophysiology of PCC/PGL is important for diagnosis,and identifying risk of malignancy or recurrent disease,and it is also helpful to optimize treatments and surveillance for both the patient and family members and to provide effective genetic advice in genetic counselling.

关 键 词：嗜铬细胞瘤/副神经节瘤 SDHx 基因型 表现型 "伪缺氧"信号转导通路 激酶信号转导通路 

分 类 号：R736.6[医药卫生—肿瘤]