Dataset Information

Inactivating mutations in GNA13 and RHOA in Burkitt's lymphoma and diffuse large B-cell lymphoma: a tumor suppressor function for the Gα13/RhoA axis in B cells.

ABSTRACT: 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 Gα13, in Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL). We found that mutations in the downstream target of Gα13, 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 Gα13 in B-cell lymphoma cells with mutant GNA13 has limited impact in vitro but results in a remarkable growth inhibition in vivo. Thus, although Gα13 and RhoA activity has previously been linked to cellular transformation and metastatic potential of epithelial cancers, our findings support a tumor suppressive role for Gα13 and RhoA in Burkitt's lymphoma and DLBCL.

SUBMITTER: O'Hayre M

PROVIDER: S-EPMC4885800 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inactivating mutations in GNA13 and RHOA in Burkitt's lymphoma and diffuse large B-cell lymphoma: a tumor suppressor function for the Gα13/RhoA axis in B cells.

O'Hayre M M Inoue A A Kufareva I I Wang Z Z Mikelis C M CM Drummond R A RA Avino S S Finkel K K Kalim K W KW DiPasquale G G Guo F F Aoki J J Zheng Y Y Lionakis M S MS Molinolo A A AA Gutkind J S JS

Oncogene 20151130 29

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 cont ...[more]

PMID: 26616858

Similar Datasets

Project description:BackgroundBurkitt's lymphoma is an aggressive B-cell lymphoma that occurs in children and adults and is largely curable with the use of intensive and toxic chemotherapy. Current treatments are less effective and have more severe side effects in adults and patients with immunodeficiency than in children.MethodsWe studied low-intensity treatment consisting of infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (EPOCH-R) in patients with untreated Burkitt's lymphoma. Two EPOCH-R regimens were tested: a standard dose-adjusted combination in human immunodeficiency virus (HIV)-negative patients (DA-EPOCH-R group) and a lower-dose short-course combination with a double dose of rituximab in HIV-positive patients (SC-EPOCH-RR group).ResultsA total of 30 consecutive patients were treated; 19 patients were in the DA-EPOCH-R group, and 11 in the SC-EPOCH-RR group. The overall median age of the patients was 33 years, and 40% were 40 years of age or older; 73% of the patients had intermediate-risk disease, and 10% had high-risk disease. The principal toxic events, fever and neutropenia, were observed during 22% of the DA-EPOCH-R treatment cycles and 10% of the SC-EPOCH-RR treatment cycles. The tumor lysis syndrome developed in 1 patient; no treatment-related deaths occurred. The median cumulative doses of doxorubicin-etoposide and cyclophosphamide administered in the SC-EPOCH-RR group were 47% and 57% lower, respectively, than those administered in the DA-EPOCH-R group. With median follow-up times of 86 months in the DA-EPOCH-R group and 73 months in the SC-EPOCH-RR group, the rates of freedom from progression of disease and overall survival were, respectively, 95% and 100% with DA-EPOCH-R and 100% and 90% with SC-EPOCH-RR. None of the patients died from Burkitt's lymphoma.ConclusionsIn this uncontrolled prospective study, low-intensity EPOCH-R-based treatment was highly effective in adults with sporadic or immunodeficiency-associated Burkitt's lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov numbers, NCT00001337 and NCT00006436.).

Dataset Information

Inactivating mutations in GNA13 and RHOA in Burkitt's lymphoma and diffuse large B-cell lymphoma: a tumor suppressor function for the Gα13/RhoA axis in B cells.

Publications

Inactivating mutations in GNA13 and RHOA in Burkitt's lymphoma and diffuse large B-cell lymphoma: a tumor suppressor function for the Gα13/RhoA axis in B cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets