Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome

Cao, Yanan, He, Minghui, Gao, Zhibo, Peng, Ying, Li, Yanli, Li, Lin, Zhou, Weiwei, Li, Xiangchun, Zhong, Xu, Lei, Yiming, Su, Tingwei, Wang, Hang, Jiang, Yiran, Yang, Lin, Wei, Wei, Yang, Xu, Jiang, Xiuli, Liu, Li, He, Juan, Ye, Junna, Wei, Qing, Li, Yingrui, Wang, Weiqing, Wang, Jun and Ning, Guang (2014) Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome. Science, 344 6186: 913-917. doi:10.1126/science.1249480

Author Cao, Yanan
He, Minghui
Gao, Zhibo
Peng, Ying
Li, Yanli
Li, Lin
Zhou, Weiwei
Li, Xiangchun
Zhong, Xu
Lei, Yiming
Su, Tingwei
Wang, Hang
Jiang, Yiran
Yang, Lin
Wei, Wei
Yang, Xu
Jiang, Xiuli
Liu, Li
He, Juan
Ye, Junna
Wei, Qing
Li, Yingrui
Wang, Weiqing
Wang, Jun
Ning, Guang
Title Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome
Formatted title
Activating hotspot L205R mutation in PRKACA and adrenal Cushing's syndrome
Journal name Science   Check publisher's open access policy
ISSN 1095-9203
Publication date 2014-05-23
Year available 2014
Sub-type Article (original research)
DOI 10.1126/science.1249480
Open Access Status Not yet assessed
Volume 344
Issue 6186
Start page 913
End page 917
Total pages 5
Place of publication Washington, DC, United States
Publisher American Association for the Advancement of Science
Language eng
Formatted abstract
Adrenal Cushing's syndromeis caused by excess production of glucocorticoid from adrenocortical tumors and hyperplasias, which leads to metabolic disorders. We performed whole-exome sequencing of 49 blood-tumor pairs and RNA sequencing of 44 tumors from cortisol-producing adrenocortical adenomas (ACAs), adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasias (AIMAHs), and adrenocortical oncocytomas (ADOs). We identified a hotspot in the PRKACA gene with a L205R mutation in 69.2% (27 out of 39) of ACAs and validated in 65.5% of a total of 87 ACAs. Our data revealed that the activating L205R mutation, which locates in the P+1 loop of the protein kinase A (PKA) catalytic subunit, promoted PKA substrate phosphorylation and target gene expression. Moreover, we discovered the recurrently mutated gene DOT1L in AIMAHs and CLASP2 in ADOs. Collectively, these data highlight potentially functional mutated genes in adrenal Cushing's syndrome.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 61 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 64 times in Scopus Article | Citations
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