title: t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth.
abstract: 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.
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Ellen
authors.initials: E
authors.lastname: McPhail
authors.forename: Michelle
authors.initials: M
authors.lastname: Manske
authors.forename: Esteban
authors.initials: E
authors.lastname: Braggio
authors.forename: Tammy
authors.initials: T
authors.lastname: Price-Troska
authors.forename: Steven
authors.initials: S
authors.lastname: Ziesmer
authors.forename: Frank
authors.initials: F
authors.lastname: Secreto
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Mamta
authors.initials: M
authors.lastname: Gupta
authors.forename: Mark
authors.initials: M
authors.lastname: Law
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: Martin J S
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Anne J
authors.initials: AJ
authors.lastname: Novak
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056905:Chromosome Breakpoints; D002883:Chromosomes, Human, Pair 14; D041321:Chromosomes, Human, X; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023061:Gene Order; D006367:HeLa Cells; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008969:Molecular Sequence Data; D049312:Receptors, Lysophospholipid / Q000235:genetics* / Q000378:metabolism; D055751:SOXC Transcription Factors / Q000235:genetics; D015398:Signal Transduction; D014178:Translocation, Genetic
chemical_list: C118065:G-protein-coupled receptor 34; D049312:Receptors, Lysophospholipid; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3