Inactivating mutations in GNA13 and RHOA in Burkitt's lymphoma and diffuse large B-cell lymphoma: a tumor suppressor function for the G[alpha].sub.13/RhoA axis in B cells

G proteins and their cognate G protein-coupled receptors (GPCRs) function as critical signal transduction molecules that regulate cell survival, proliferation, motility and differentiation. The aberrant expression and/or function of these molecules have been linked to the growth, progression and met...

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Bibliographic Details
Published in:Oncogene 2016-07, Vol.35 (29), p.3771
Main Authors: O'Hayre, M, Inoue, A, Kufareva, I, Wang, Z, Mikelis, C M, Drummond, R A, Avino, S
Format: Article
Language:English
Subjects:
Burkitt's lymphoma
Care and treatment
Cell receptors
Development and progression
Gene mutations
Genetic aspects
Health aspects
Tumor suppressor genes
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Summary:G proteins and their cognate G protein-coupled receptors (GPCRs) function as critical signal transduction molecules that regulate cell survival, proliferation, motility and differentiation. The aberrant expression and/or function of these molecules have been linked to the growth, progression and metastasis of various cancers. As such, the analysis of mutations in the genes encoding GPCRs, G proteins and their downstream targets provides important clues regarding how these signaling cascades contribute to malignancy. Recent genome-wide sequencing efforts have unveiled the presence of frequent mutations in GNA13, the gene encoding the G protein G[alpha].sub.13, in Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL). We found that mutations in the downstream target of G[alpha].sub.13, RhoA, are also present in Burkitt's lymphoma and DLBCL. By multiple complementary approaches, we now show that that these cancer-specific GNA13 and RHOA mutations are inhibitory in nature, and that the expression of wild-type G[alpha].sub.13 in B-cell lymphoma cells with mutant GNA13 has limited impact in vitro but results in a remarkable growth inhibition in vivo. Thus, although G[alpha].sub.13 and RhoA activity has previously been linked to cellular transformation and metastatic potential of epithelial cancers, our findings support a tumor suppressive role for G[alpha].sub.13 and RhoA in Burkitt's lymphoma and DLBCL.
ISSN:0950-9232
1476-5594
DOI:10.1038/onc.2015.442