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Recurrent GNAQ mutation encoding T96S in natural killer/T cell lymphoma
- Source :
- Nature Communications, Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019)
- Publication Year :
- 2019
- Publisher :
- Nature Publishing Group UK, 2019.
-
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.<br />Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive disease. Here, the authors identify recurrent somatic mutations of GNAQ in NKTCL, and model how this mutation contributes to NKTCL pathogenesis.
- Subjects :
- 0301 basic medicine
Cell death
Uveal Neoplasms
Somatic cell
Science
General Physics and Astronomy
Biology
medicine.disease_cause
General Biochemistry, Genetics and Molecular Biology
Article
Pathogenesis
03 medical and health sciences
Cell growth
0302 clinical medicine
Conditional gene knockout
medicine
Cancer genomics
T-cell lymphoma
Humans
lcsh:Science
Cancer genetics
Mutation
Multidisciplinary
General Chemistry
Genomics
medicine.disease
Natural killer T cell
GTP-Binding Protein alpha Subunits
Lymphoma
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
GTP-Binding Protein alpha Subunits, Gq-G11
lcsh:Q
Artifacts
GNAQ
Pseudogenes
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....f4a0b59cf1f58a1b32cc14b33ffc6e32