Abstract G-proteins and their cognate G-protein coupled receptors (GPCRs) are critical signal transduction molecules that regulate cell survival, proliferation, motility and differentiation. The aberrant expression or function of these molecules has been linked to growth, progression and metastasis of various cancers. Recent genome-wide sequencing efforts have unveiled numerous previously uncharacterized mutations in G-proteins and GPCRs, which could have significant implications to cancer initiation and progression. Of interest, recent analyses have demonstrated that there are frequent mutations in GNA13 in Burkitt's lymphoma and Diffuse Large B cell lymphomas (DLBCL) that are highly statistically significant over background cancer gene mutation rate, and occur in ∼10-13% of patients with these lymphomas. Mutations in the downstream target of G13, RhoA, are also present in several Burkitt's lymphoma tumors, highlighting that mutations in this G13-RhoA pathway may be key to the oncogenic potential of these B cell lymphomas. Although G13 activity has previously been linked cellular transformation and metastatic potential of epithelial cancers, our data suggests that the mutations in GNA13 in these B cell lymphomas are mostly inhibitory in nature. Thus, we have functionally characterized several mutations in GNA13 and RHOA found in Burkitt's lymphoma and DLBCL. Citation Format: Morgan L. O'Hayre, Irina Kufareva, Jose P. Vaqué, Miguel A. Piris, J. Silvio Gutkind. Deciphering the effects of GNA13 mutations in B-cell lymphomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4202. doi:10.1158/1538-7445.AM2014-4202