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t(X;14)(p11.4;q32.33) IGH/GPR34

Written2013-08Iwona Wlodarska
Center for Human Genetics, KU Leuven, Leuven, Belgium

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
Atlas_Id 1637
 
  Figure 1. Partial karyotype of t(X;14)(p11.4;q32.33). Duplication of der(14) occurs recurrently in t(X;14)-positive cases.

Clinics and Pathology

Disease B-cell non Hodgkin's lymphoma, including mucosa-associated lymphoid tissue (MALT) lymphoma, nodal marginal zone lymphoma (nMZL) and gastric diffuse large B-cell lymphoma (DLBCL)
Etiology Five cases have been reported so far: three females aged 60-69 years with primary MALT lymphoma involving the lung (two cases) and the parotid gland (one case), one 82-years old female with nMZL and one 82-years old male with gastric DLBCL. All patients had an underlying disorder, including Sjögren syndrome, a leukocytoclastic vasculitis and polyneuropathy, and Helicobacter Pylori-negative chronic gastritis with intestinal metaplasia. t(X;14)(p11.4;q32.33) is a rare translocation, being identified in 2 of 61 (3.3%) cases of MALT lymphoma, in one of 43 (2.3%) cases of nMZL and one of 19 (5.2) cases of extranodal DLBCL with clonal chromosomal abnormalities collected in Center for Human Genetics, KU Leuven, Leuven, Belgium (Baens et al., 2012). t(X;14)/IGH-GPR34 and the well known t(1;14)/IGH-BCL10, t(3;14)/IGH-FOXP1, t(11;18)/API2-MALT1 and t(14;18)/IGH-MALT1 are mutually exclusive in MALT lymphoma.
Prognosis Unknown so far.

Cytogenetics

Cytogenetics Molecular FISH and molecular studies demonstrated involvement of IGH/14q32.33 (Fig. 2a) and the GPR34 gene at Xp11.4 (Fig. 2b).
 
  Figure 2. FISH analysis of t(X;14)(p11.4;q32.33). Applied probes: (a) LSI IGH; (b) BAC clones flanking the Xp11.4 breakpoint (RP11-204C16/red and RP11-1174J21/green) (Baens et al., 2012).
Additional anomalies Cytogenetic data are available in four cases. The translocation occurred as the sole aberration in one case and was accompanied by 2 to 4 additional chromosomal abnormalities in the remaining cases. Subclonal duplication of der(14)t(X;14) or extra copy of IGH-GPR34 were found in three reported cases.

Genes involved and Proteins

Gene Name GPR34
Location Xp11.4
Note Alias: G Protein-Coupled Receptor 34.
Dna / Rna GPR34 consists of 3 exons, but only one is protein coding exon. Transcript length: 1924 bps. Transcription is from centromere to telomere. GPR34 and the neighboring GPR82 are housed by intron 5 of CASK. Expression of GPR34 mRNA is ubiquitous in human tissues.
Protein GPR34 codes for a G protein-coupled receptor that belongs to the largest family of cell surface molecules involved in signal transmission. These integral membrane proteins contain 7 putative transmembrane domains and mediate signals to the interior of the cell. The predicted 381-amino acid GPR34 has a calculated relative molecular mass of approximately 44 kDa, potential N-glycosylation sites within the extracellular N-terminal region, consensus acceptor phosphorylation sites for protein kinase A and C, and potential receptor-specific kinase phosphorylation sites (multiple serine and threonine residues). The receptor encoded by GPR34 is most similar to the PY2 receptor subfamily of GPCR and it is evolutionarily conserved being present in all vertebrate classes. GPR34 protein is ubiquitously expressed; its highest levels of expression were found in placenta, spleen and brain (Engemaier et al., 2006). Experimental data suggest that GPR34 is required for adequate immune responses to antigen and pathogen contact. The natural ligand of GPR34 and downstream signaling pathways are largely unknown.
Gene Name IGH
Location 14q32.33

Result of the chromosomal anomaly

Hybrid gene
Note Sequence analysis of one case with t(X;14)(p11.4;q32.33) showed that the Xp11.4 breakpoint fell between exon 1 and 2 of GPR82, the gene located in close vicinity to GPR34, and the 14q32.33 breakpoint occurred in the IGHA2 switch region, placing both genes in close proximity to the IGHA2 3' regulatory region enhancers, HS4, HS1, HS2, and HS3 (Ansell et al., 2012). Overexpression of GPR34 mRNA, but not GPR82 and CASK, indicates that the translocation targets GPR34. The functional consequences of the translocation remain elusive. Experimental data of Ansell et al. (2012) indicate that overexpression of GPR34 leads to constitutive activation of the ERK pathway, and also implicate a role of GPR34 in the activation of CREB, AP-1, PKC and NF-kB. Activation of NF-kB and ERK by GPR34, however, was not confirmed by Baens et al. (2012).
  

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth.
Ansell SM, Akasaka T, McPhail E, Manske M, Braggio E, Price-Troska T, Ziesmer S, Secreto F, Fonseca R, Gupta M, Law M, Witzig TE, Dyer MJ, Dogan A, Cerhan JR, Novak AJ.
Blood. 2012 Nov 8;120(19):3949-57. doi: 10.1182/blood-2011-11-389908. Epub 2012 Sep 10.
PMID 22966169
 
t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34.
Baens M, Finalet Ferreiro J, Tousseyn T, Urbankova H, Michaux L, de Leval L, Dierickx D, Wolter P, Sagaert X, Vandenberghe P, De Wolf-Peeters C, Wlodarska I.
Haematologica. 2012 Feb;97(2):184-8. doi: 10.3324/haematol.2011.052639. Epub 2011 Nov 4.
PMID 22058210
 
Genomic and supragenomic structure of the nucleotide-like G-protein-coupled receptor GPR34.
Engemaier E, Rompler H, Schoneberg T, Schulz A.
Genomics. 2006 Feb;87(2):254-64. Epub 2005 Dec 9.
PMID 16338117
 

Citation

This paper should be referenced as such :
Wlodarska, I
t(X;14)(p11.4;q32.33) IGH/GPR34
Atlas Genet Cytogenet Oncol Haematol. 2014;18(2):122-124.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/tX14p11q32ID1637.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(X;14)(p11.4;q32.33) IGH/GPR34

External links

arrayMap (UZH-SIB Zurich)IGH (14q32.33) GPR34 (Xp11.4)

Mitelman databaset(X;14)(p11.4;q32.33) [Case List]    t(X;14)(p11.4;q32.33) [Association List] Mitelman database (CGAP - NCBI)
arrayMap[select an item]
 
Mitelman databaseIGH/GPR34 [MCList]  IGH (14q32.33) GPR34 (Xp11.4)
 
Disease databaset(X;14)(p11.4;q32.33) IGH/GPR34
REVIEW articlesautomatic search in PubMed
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