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

Nat Commun. 2019 Sep 16;10(1):4209. doi: 10.1038/s41467-019-12032-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • GTP-Binding Protein alpha Subunits, Gq-G11 / genetics*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / immunology
  • Humans
  • Lymphoma, T-Cell / genetics*
  • Lymphoma, T-Cell / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation, Missense*
  • Natural Killer T-Cells / immunology


  • GTP-Binding Protein alpha Subunits, Gq-G11