Identification of recurrent USP48 and BRAF mutations in Cushing's disease

doi:10.1038/s41467-018-05275-5

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Identification of recurrent USP48 and BRAF mutations in Cushing's disease
	Chen, Jianhua 2,3,4,5; Jian, Xuemin 2,3,4,5; Deng, Siyu 6; Ma, Zengyi 7,8,9; Shou, Xuefei 7,8,9; Shen, Yue 7,8,9; Zhang, Qilin 7,8,9; Song, Zhijian 2,3,4,5; Li, Zhiqiang 2,3,4,5; Peng, Hong 6
刊名	NATURE COMMUNICATIONS
	2018-08-09
卷号	9
ISSN号	2041-1723
DOI	10.1038/s41467-018-05275-5
文献子类	Article
英文摘要	Cushing's disease results from corticotroph adenomas of the pituitary that hypersecrete adrenocorticotropin (ACTH), leading to excess glucocorticoid and hypercortisolism. Mutations of the deubiquitinase gene USP8 occur in 35-62% of corticotroph adenomas. However, the major driver mutations in USP8 wild-type tumors remain elusive. Here, we report recurrent mutations in the deubiquitinase gene USP48 (predominantly encoding p.M415I or p.M415V; 21/91 subjects) and BRAF (encoding p.V600E; 15/91 subjects) in corticotroph adenomas with wild-type USP8. Similar to USP8 mutants, both USP48 and BRAF mutants enhance the promoter activity and transcription of the gene encoding proopiomelanocortin (POMC), which is the precursor of ACTH, providing a potential mechanism for ACTH overproduction in corticotroph adenomas. Moreover, primary corticotroph tumor cells harboring BRAF V600E are sensitive to the BRAF inhibitor vemurafenib. Our study thus contributes to the understanding of the molecular mechanism of the pathogenesis of corticotroph adenoma and informs therapeutic targets for this disease.
资助项目	National Key Basic Research Program of China (973 Program)[2015CB559100] ; National Natural Science Foundation of China[31325014] ; National Natural Science Foundation of China[81421061] ; National Natural Science Foundation of China[81501154] ; Program of Shanghai Academic Research Leader[15XD1502200] ; National Key RD Program[2016YFC1201701] ; National Key R&D Program-Special Project on Precision Medicine[2016YFC0903402] ; Shanghai Key Laboratory of Psychotic Disorders[13DZ2260500] ; Research Project of Shanghai Health and Family Planning Commission[201440552] ; 1000-Youth Elite Program and Shanghai Pujiang Scholar[5PJ1407400] ; China Pituitary Adenoma Specialist Council (CPASC)[00000000] ; National High Technology Research and Development Program of China (863 program)[2014AA020611] ; Chang Jiang Scholars Program[00000000] ; National Program for Support of Top-notch Young Professionals[00000000] ; National Science Fund for Distinguished Young Scholars[81725011] ; Shanghai Rising-Star Tracking Program[12QH1400400]
WOS关键词	HUMAN CANCER ; PROOPIOMELANOCORTIN GENE ; DEUBIQUITINATING ENZYME ; PITUITARY-ADENOMAS ; KAPPA-B ; TRANSCRIPTION ; ACTIVATION ; RAF ; PATHWAYS ; GENOME
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000441157600006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279622]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Zhao, Yao; Huang, Chuanxin; Shi, Yongyong
作者单位	1.Qingdao Univ, Affiliated Hosp, Qingdao 266003, Shandong, Peoples R China; 2.Shanghai Jiao Tong Univ, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai Key Lab Psychot Disorders,BioX Inst, Shanghai Mental Hlth Ctr,Sch Med,Minist Educ, Shanghai 200030, Peoples R China; 3.Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200030, Peoples R China; 4.Shanghai Jiao Tong Univ, Dept Otolaryngol Head & Neck Surg, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China; 5.Shanghai Jiao Tong Univ, Ctr Sleep Med, Shanghai 200233, Peoples R China; 6.Shanghai Jiao Tong Univ, Shanghai Inst Immunol, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ,Sch Med, Shanghai 200025, Peoples R China; 7.Fudan Univ, Shanghai Med Coll, Huashan Hosp, Dept Neurosurg, Shanghai 200040, Peoples R China; 8.Shanghai Pituitary Tumor Ctr, Shanghai 200040, Peoples R China; 9.Fudan Univ, Inst Neurosurg, Shanghai 200040, Peoples R China; 10.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Innovat Ctr Cell Signaling Network, CAS Key Lab Syst Biol,CAS Ctr Excellence Mol Cell, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Chen, Jianhua,Jian, Xuemin,Deng, Siyu,et al. Identification of recurrent USP48 and BRAF mutations in Cushing's disease[J]. NATURE COMMUNICATIONS,2018,9.
APA	Chen, Jianhua.,Jian, Xuemin.,Deng, Siyu.,Ma, Zengyi.,Shou, Xuefei.,...&Shi, Yongyong.(2018).Identification of recurrent USP48 and BRAF mutations in Cushing's disease.NATURE COMMUNICATIONS,9.
MLA	Chen, Jianhua,et al."Identification of recurrent USP48 and BRAF mutations in Cushing's disease".NATURE COMMUNICATIONS 9(2018).