Recurrent GNAQ mutation encoding T96S in natural killer/T cell lymphoma
Recurrent GNAQ mutation encoding T96S in natural killer/T cell lymphoma
复制标题
自然杀伤/T 细胞淋巴瘤中编码 T96S 的复发性 GNAQ 突变
DOI：
10.1038/s41467-019-12032-9
复制
发表时间：
2019-09-16
影响因子：
16.6
通讯作者：
Zhang, Mingzhi
中科院分区：
文献类型：
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作者：
Li, Zhaoming;Zhang, Xudong;Zhang, Mingzhi
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 ofGNAQ(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 withGNAQT96S mutations have inferior survival. Taken together, we identify recurrent somaticGNAQT96S 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.
