Recurrent GNAQ mutation encoding T96S in natural killer/T cell lymphoma

Zhaoming Li, Xudong Zhang, Weili Xue, Yanjie Zhang, Chaoping Li, Yue Song, Mei Mei, Lisha Lu, Yingjun Wang, Zhiyuan Zhou, Mengyuan Jin, Yangyang Bian, Lei Zhang, Xinhua Wang, Ling Li, Xin Li, Xiaorui Fu, Zhenchang Sun, Jingjing Wu, Feifei Nan, Yu Chang, Jiaqin Yan, Hui Yu, Xiaoyan Feng, Guannan Wang, Dandan Zhang, Xuefei Fu, Yuan Zhang, Ken H. Young, Wencai Li () and Mingzhi Zhang ()
Additional contact information
Zhaoming Li: The First Affiliated Hospital of Zhengzhou University
Xudong Zhang: The First Affiliated Hospital of Zhengzhou University
Weili Xue: The First Affiliated Hospital of Zhengzhou University
Yanjie Zhang: The First Affiliated Hospital of Zhengzhou University
Chaoping Li: The First Affiliated Hospital of Zhengzhou University
Yue Song: The First Affiliated Hospital of Zhengzhou University
Mei Mei: The First Affiliated Hospital of Zhengzhou University
Lisha Lu: The First Affiliated Hospital of Zhengzhou University
Yingjun Wang: The First Affiliated Hospital of Zhengzhou University
Zhiyuan Zhou: The First Affiliated Hospital of Zhengzhou University
Mengyuan Jin: The First Affiliated Hospital of Zhengzhou University
Yangyang Bian: The First Affiliated Hospital of Zhengzhou University
Lei Zhang: The First Affiliated Hospital of Zhengzhou University
Xinhua Wang: The First Affiliated Hospital of Zhengzhou University
Ling Li: The First Affiliated Hospital of Zhengzhou University
Xin Li: The First Affiliated Hospital of Zhengzhou University
Xiaorui Fu: The First Affiliated Hospital of Zhengzhou University
Zhenchang Sun: The First Affiliated Hospital of Zhengzhou University
Jingjing Wu: The First Affiliated Hospital of Zhengzhou University
Feifei Nan: The First Affiliated Hospital of Zhengzhou University
Yu Chang: The First Affiliated Hospital of Zhengzhou University
Jiaqin Yan: The First Affiliated Hospital of Zhengzhou University
Hui Yu: The First Affiliated Hospital of Zhengzhou University
Xiaoyan Feng: The First Affiliated Hospital of Zhengzhou University
Guannan Wang: The First Affiliated Hospital of Zhengzhou University
Dandan Zhang: The First Affiliated Hospital of Zhengzhou University
Xuefei Fu: Novogene Bioinformatics Technology Co, Ltd
Yuan Zhang: The Academy of Medical Science of Zhengzhou University
Ken H. Young: The University of Texas MD Anderson Cancer Center
Wencai Li: The First Affiliated Hospital of Zhengzhou University
Mingzhi Zhang: The First Affiliated Hospital of Zhengzhou University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive malignancy with a higher prevalence in Asia and South America. However, the molecular genetic mechanisms underlying NKTCL remain unclear. Here, we identify somatic mutations of GNAQ (encoding the T96S alteration of Gαq protein) in 8.7% (11/127) of NKTCL patients, through whole-exome/targeted deep sequencing. Using conditional knockout mice (Ncr1-Cre-Gnaqfl/fl), we demonstrate that Gαq deficiency leads to enhanced NK cell survival. We also find that Gαq suppresses tumor growth of NKTCL via inhibition of the AKT and MAPK signaling pathways. Moreover, the Gαq T96S mutant may act in a dominant negative manner to promote tumor growth in NKTCL. Clinically, patients with GNAQ T96S mutations have inferior survival. Taken together, we identify recurrent somatic GNAQ T96S mutations that may contribute to the pathogenesis of NKTCL. Our work thus has implications for refining our understanding of the genetic mechanisms of NKTCL and for the development of therapies.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12032-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12032-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12032-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().