t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth

Stephen Maxted Ansell, Takashi Akasaka, Ellen McPhail, Michelle Manske, Esteban D Braggio, Tammy Price-Troska, Steven Ziesmer, Frank Secreto, Rafael Fonseca, Mamta Gupta, Mark Law, Thomas Elmer Witzig, Martin J S Dyer, Ahmet Dogan, James R Cerhan, Anne J Novak

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3949-3957
Number of pages9
JournalBlood
Volume120
Issue number19
DOIs
StatePublished - Nov 8 2012

Fingerprint

Marginal Zone B-Cell Lymphoma
Cell growth
Tumors
Lymphoma
Growth
Neoplasms
Phosphorylation
Cloning
Mitogen-Activated Protein Kinase Kinases
Cell proliferation
Transcription
Chromosomes
G-Protein-Coupled Receptors
Aberrations
Gene expression
Brain
Genes
Cells
Tissue
X Chromosome

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth. / Ansell, Stephen Maxted; Akasaka, Takashi; McPhail, Ellen; Manske, Michelle; Braggio, Esteban D; Price-Troska, Tammy; Ziesmer, Steven; Secreto, Frank; Fonseca, Rafael; Gupta, Mamta; Law, Mark; Witzig, Thomas Elmer; Dyer, Martin J S; Dogan, Ahmet; Cerhan, James R; Novak, Anne J.

In: Blood, Vol. 120, No. 19, 08.11.2012, p. 3949-3957.

Research output: Contribution to journalArticle

Ansell, Stephen Maxted ; Akasaka, Takashi ; McPhail, Ellen ; Manske, Michelle ; Braggio, Esteban D ; Price-Troska, Tammy ; Ziesmer, Steven ; Secreto, Frank ; Fonseca, Rafael ; Gupta, Mamta ; Law, Mark ; Witzig, Thomas Elmer ; Dyer, Martin J S ; Dogan, Ahmet ; Cerhan, James R ; Novak, Anne J. / t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth. In: Blood. 2012 ; Vol. 120, No. 19. pp. 3949-3957.
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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.",
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AU - Akasaka, Takashi

AU - McPhail, Ellen

AU - Manske, Michelle

AU - Braggio, Esteban D

AU - Price-Troska, Tammy

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AU - Gupta, Mamta

AU - Law, Mark

AU - Witzig, Thomas Elmer

AU - Dyer, Martin J S

AU - Dogan, Ahmet

AU - Cerhan, James R

AU - Novak, Anne J

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