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Biochemistry and Molecular Medicine Faculty Publications
t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth
Stephen M. Ansell, Mayo Clinic
Takashi Akasaka, University of Leicester
Ellen McPhail, Mayo Clinic
Michelle Manske, Mayo Clinic
Esteban Braggio, Mayo Clinic Scottsdale-Phoenix, Arizona
Tammy Price-Troska, Mayo Clinic
Steven Ziesmer, Mayo Clinic
Frank Secreto, Mayo Clinic
Rafael Fonseca, Mayo Clinic Scottsdale-Phoenix, Arizona
Mamta Gupta, Mayo Clinic
Mark Law, Mayo Clinic
Thomas E. Witzig, Mayo Clinic
Martin J.S. Dyer, University of Leicester
Ahmet Dogan, Mayo Clinic
James R. Cerhan, Mayo Clinic
Anne J. Novak, Mayo Clinic
10.1182/blood-2011-11-389908
Genetic aberrations, including trisomies 3 and 18, and well-defined IGH translocations, have been described in marginal zone lymphomas (MZLs); however, these known genetic events are present in only a subset of cases. Here, we report the cloning of an IGH translocation partner on chromosome X, t(X;14)(p11.4;q32) that deregulates expression of an poorly characterized orphan G-protein-coupled receptor, GPR34. Elevated GPR34 gene expression was detected independent of the translocation in multiple subtypes of non-Hodgkin lymphoma and distinguished a unique molecular subtype of MZL. Increased expression of GPR34 was also detected in tissue from brain tumors and surface expression of GPR34 was detected on human MZL tumor cells and normal immune cells. Overexpression of GPR34 in lymphoma and HeLa cells resulted in phosphorylation of ERK, PKC, and CREB; induced CRE, AP1, and NF-κB- mediated gene transcription; and increased cell proliferation. In summary, these results are the first to identify a role for a GPR34 in lymphoma cell growth, provide insight into GPR34-mediated signaling, identify a genetically unique subset of MZLs that express high levels of GPR34, and suggest that MEK inhibitors may be useful for treatment of GPR34-expressing tumors. © 2012 by The American Society of Hematology.
Ansell, S., Akasaka, T., McPhail, E., Manske, M., Braggio, E., Price-Troska, T., Ziesmer, S., Secreto, F., Fonseca, R., Gupta, M., Law, M., Witzig, T., Dyer, M., Dogan, A., Cerhan, J., & Novak, A. (2012). t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth. Blood, 120 (19). http://dx.doi.org/10.1182/blood-2011-11-389908