垂体生长激素腺瘤遗传学研究进展  

An update on the genetics of pituitary growth hormone adenoma

作　　者：苗卉 朱惠娟 Hui Miao;Huijuan Zhu(Translational Medicine Center,National Key Laboratory for Rare Disease Research,Key Laboratory of Endocrinology of National Health Commission,Department of Endocrinology,Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院,北京协和医院内分泌科,卫健委内分泌重点实验室,国家罕见病重点实验室,转化医学中心,100730

出　　处：《中华内分泌代谢杂志》2021年第12期1121-1126,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家重点研发计划(2016YFC0901501)。

摘　　要：垂体生长激素腺瘤是一种鞍区良性肿瘤,因高分泌生长激素导致临床出现肢端肥大症或巨人症等表现。随着基因诊断技术的发展,发现多种基因遗传学变异参与生长激素腺瘤的发病,并与患者的临床表型及治疗反应相关,推动了垂体生长激素腺瘤的精准诊治。GNAS的体细胞激活突变可见于40%的生长激素腺瘤,嵌合突变可导致McCune-Albright综合征,最常见的垂体表现为生长激素的过度分泌。芳烃受体相互作用蛋白(AIP)的胚系突变可见于家族性及散发性生长激素腺瘤,突变患者多为早期起病的大腺瘤,且生长抑素治疗效果欠佳。涉及GPR101基因的Xq26.3微重复引起X连锁的肢端肥大巨人症。生长激素腺瘤既可以作为散发的孤立性垂体腺瘤,也可以作为综合征疾病的一部分,例如多发性内分泌腺瘤病1型(MEN1)和4型(MEN4)、Carney综合征等。本综述总结了垂体生长激素腺瘤的遗传学研究进展,以期增加临床医师对孤立性及综合征性垂体生长激素腺瘤的认识,推动垂体生长激素腺瘤的机制和治疗靶点研究等。Pituitary growth hormone adenoma is a benign tumor in sellar region,which presents clinical manifestations of acromegaly or gigantism due to excessive secretion of growth hormone.With the development of genetic technology,a variety of genetic variations are identified being involved in the pathogenesis of growth hormone adenoma and their clinical phenotypes as well as treatment responses,which promotes precise diagnosis and management of pituitary growth hormone adenomas.Among somatic mutations,activating somatic mutations of GNAS can be found in 40%of growth hormone adenomas.Mosaic mutations of GNAS lead to McCune-Albright syndrome,and the most common pituitary features is excessive secretion of growth hormone.Germline mutations of aryl hydrocarbon receptor interacting protein(AIP)can be found in familial and sporadic growth hormone adenomas.AIP-mutated adenomas usually are early-onset macroadenoma with poor response to somatostatin therapy.Xq26.3 microduplication involving the gene GPR101 causes X-linked acrogigantism.Growth hormone adenoma can present as a sporadic solitary pituitary adenoma,or as a part of syndromic disease such as multiple endocrine neoplasia type 1(MEN1)and type 4(MEN4),Carney syndrome,etc.This article summarized the progress of genetic research on growth hormone adenoma,to increase understanding of solitary and syndromic pituitary growth hormone adenomas,and promote further exploration of mechanism and potential therapy targets of pituitary growth hormone adenomas.

关 键 词：垂体生长激素腺瘤 生长激素 基因 遗传学变异 

分 类 号：R736.4[医药卫生—肿瘤]