t(1;14)(q21;q32) FCRL4/IGH

2004-12-01   Mary Callanan , Dominique Leroux 

1.Lymphoma Research Group - Groupe de Recherche sur les Lymphomes - EMI0353, Institut Albert Bonniot, Université Joseph Fourier Grenoble 1, La Tronche 38706, France
2.Lymphoma Research Group - Groupe de Recherche sur les Lymphomes - EMI0353, Institut Albert Bonniot, Université Joseph Fourier Grenoble 1, La Tronche 38706, France

Clinics and Pathology

Disease

Multiple Myeloma and B-cell non-Hodgkins lymphoma

Epidemiology

Rare. 2 published cases : 1 in a multiple myeloma cell line. The second in a case of gastric diffuse large B-cell lymphoma (DLBCL).

Prognosis

Unknown

Note

The t(1;14) interrupts the IRTA gene locus (Immunoglobulin superfamily Receptor Translocation Associated gene locus) which spans approximately 250kb, between the IRTA1 and IRTA2 genes.

Genes Involved and Proteins

Gene name
FCRL4 (Fc receptor like 4)
Location
1q23.1
Dna rna description
IRTA1 localises to the IRTA gene locus. Three IRTA1 transcripts of 2.5kb, 2.7kb and 3.5kb are possible due to alternate usage of 3 polyadenylation sites.
Protein description
The three alternate IRTA1 transcripts give rise to the same putative 515 amino acid protein. The protein shows a signal peptide, four extracellular Ig-type domains carrying three potential asparagaine (N)-linked glycosylation sites, a 16 amino acid transmmbrane and a 106 amino acid cytoplasmic domain with three putative consensus Src-homology 2 SH2 binding domains. These domains show similarity to both ITAM (Immunoreceptor Tyrosine-based Activation Motifs) and ITIM (Immunoreceptor Tyrosine-based Inhibition Motifs). The function of the protein is unknown. It is expressed in marginal zone B cells. In the extracellular domain IRTA1 protein shows homology to Ig superfamily receptors (47% identity and 51% similarity) and Fc receptor family (37% identity and 50% similarity). In the intracellular domain, IRTA1 shows striking homology to PECAM1 (31% identity and 45% homology).
Gene name
IGH (Immunoglobulin Heavy)
Location
14q32.33

Result of the Chromosomal Anomaly

Description

Expression of IRTA1 fusion proteins. In the first case described the t(1;14) juxtaposes the IRTA1 gene to the C alpha constant gene in the same transcriptional orientation on the der(14) chromosome. An IRTA1/C alpha fusion protein results from this. The predicted fusion protein fuses the signal peptide and first two extracellular residues of IRTA1 to the C alpha encoded transmembrane and cytoplasmic domains.
Overexpression of IRTA1 was not observed in other myeloma or lymphoma cell lines, regardless of the status of its chromosomal band 1q21.
More recently long distance inverse PCR cloning identified a second case of IRTA1 translocation to IGH switch sequence (Switch gamma 3) in a case of gastric DLBCL.
In contrast, IRTA2 gene (located telomeric of IRTA1 in the IRTA gene locus) shows frequent deregulation in Burkitt lymphoma and Multiple Myeloma cell lines with 1q21 abnormalities (mostly duplications or unbalanced translocations that lead to trisomy or tetrasomy 1q).
IRTA1 is normally expressed in marginal zone B cells while IRTA2 is selectively expressed in centrocytes, marginal zone B cells and immunoblasts.
IRTA1 and 2 have been independently cloned as FcRH4 and FcRH5 (Fc Receptor Homologues) from a human lymph node cDNA library.

Bibliography

Pubmed IDLast YearTitleAuthors
114937022001Identification of a family of Fc receptor homologs with preferential B cell expression.Davis RS et al
128813172003Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT).Falini B et al
112903372001IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy.Hatzivassiliou G et al
154969802004Rapid amplification of immunoglobulin heavy chain switch (IGHS) translocation breakpoints using long-distance inverse PCR.Sonoki T et al

Summary

Note

This translocation with IRTA1 involvement is different from t(1;14)(q21;q32) with BCL9 involvement, from the t(1;14)(q21;q32) with FCGR2B involvement, and from the t(1;14)(q21;q32) with MUC1 involvement.

Citation

Mary Callanan ; Dominique Leroux

t(1;14)(q21;q32) FCRL4/IGH

Atlas Genet Cytogenet Oncol Haematol. 2004-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1375/t(1;14)(q21;q32)