t(9;14)(p13;q32)

Identity

	t(9;14)(p13;q32) (G- banding) left: Courtesy Bruce Poppe, Pascale De Paepe, Frank Speleman, right: Courtesy Jean-Luc Lai.

Clinics and Pathology

Disease	Rare recurrent chromosomal aberration, exclusively detected in B-cell lymphoproliferative disorders.
Phenotype / cell stem origin	B lymphocyte.
Epidemiology	Originally reported to be associated with a low-grade mature B-cell phenotype with plasmacytoid differentiation such as lymphoplasmacytic lymphoma, multiple myeloma/ plasma cell leukemia and chronic lymphocytic leukemia. However, the relatively frequent occurrence in diffuse large B-cell lymphoma, with or without a preceding faze of a low-grade lymphoma, suggests that this chromosomal aberration has a much wider clinical spectrum or is associated with disease progression. In addition, the t(9;14)(p13;q32) has been described occasionally in follicular lymphoma, mantle cell lymphoma and splenic marginal zone lymphoma.
Prognosis	No prognostic relevance has been attributed to the presence of the t(9;14)(p13;q32).

Cytogenetics

Cytogenetics Morphological	The t(9;14)(p13;q32) is readily recognisable with G- as well as R-banding. The presence of complex chromosomal aberrations, however, can mask the presence of this rearrangement.
	Dual and triple colour hybridisations demonstrating the presence of a t(9;14)(p13;q32) resulting in PAX5/IGH rearrangement. A,B: partial metaphase and interphase nucleus cohybridized with PAX5 locus specific probes (yellow) and dual colour interphaze cytogenetics using IgH flanking probes (red) and PAX5 locus specific probes.
Probes	Probes used for detection of PAX5 rearrangements include PAX5 spanning probes (RP11-12P15, RP11-344B23 and RP11-297B17) and a probe extending approximately up to 200kb upstream of PAX5, RP11-220I1. IgH rearrangements can be demonstrated using a commercially available dual colour probe, or IgH probes, RP11-47P23 and RP5-998D24, mapping to the IgH constant and variable regions, respectively.
Additional anomalies	No recurrent additional aberrations have been described. However, the majority of t(9;14)(p13;q32) have been reported in addition to complex chromosomal aberrations.
Variants	In addition to the t(9;14)(p13;q32), other translocations presumably involving the immunoglobulin light chain genes and PAX5 have been reported, such as the t(2;9)(p12;p13) and the t(9;22)(p13;q11).

Genes involved and Proteins

Gene Name	IgH
Location	14q32

Gene Name	PAX5
Location	9p13
Dna / Rna	The PAX5 coding region extends over a genomic interval of approximately 200kb and comprises 10 exons. Two alternative transcripts have been identified, originating from alternative promotor usage, containing exon 1A or 1B. Full length mRNA is 3650bp.
Protein	PAX5 belongs to the paired box family of transcription factors, involved in a multitude of developmental processes. PAX5 was originally identified as a B-cell specific transcription factor (hence its original name, BSAP). Recently it has been shown that PAX5 expression is continuously required in B cell lineage commitment during early B cell development.

Result of the chromosomal anomaly

Hybrid gene

Description	Translocation of the entire PAX5 gene to chromosome 14. The breakpoints at 9p13 are heterogeneous and can reside up to 200kb upstream (i.e. centromeric) of PAX5.
Detection	The variability of the chromosomal breakpoints at 9p13 as well 14q32 precludes genomic PCR approaches for detection of IgH PAX5 juxtaposition. In addition, the expression pattern of PAX5 hampers RT-PCR methods for demonstrating elevated PAX5 expression in B-cell proliferations with suspected or proven PAX5 rearrangement. Currently, the only methods for detecting IgH PAX5 juxtaposition reliably include conventional and molecular cytogenetics.

Fusion Protein

Description	In analogy to other 14q32 rearrangements, no fusion gene is created by the translocation. Rather, the genomic rearrangement leads to forced PAX5 expression.
Oncogenesis	In contrast to the novel insights in the role of PAX5 in B-cell lineage commitment, little is know on the role of PAX5 in the malignant transformation of B cells. The recent demonstration of PAX5 hypermutation in diffuse large-cell lymphomas, in addition to PAX5 overexpression associated with the t(9;14), suggest that PAX5 acts as a dominant oncogene.

External links

Other database	t(9;14)(p13;q32)	Mitelman database (CGAP - NCBI)
Other database	t(9;14)(p13;q32)	CancerChromosomes (NCBI)
Probe	and ~200kb flanking regions: RP11-12P15 (AL158148), RP11-344B23 (AL450267), RP11-297B17 (AL161781) and RP11-220I1 (AL512604).
Probe	LSI® IGH Dual Color, Break Apart Rearrangement Probe, Vysis or RP11-47P23 (AZ579057 and AQ202909) and RP5-998D24 (AZ579060 and AZ579059).

Bibliography

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Contributor(s)

Written	10-2002	Bruce Poppe, Pascale De Paepe, Frank Speleman
		Center for Medical Genetics, Ghent University Hospital MRB, De Pintelaan 185, 9000 Ghent, Belgium

Citation

This paper should be referenced as such :

Poppe B, De Paepe P, Speleman F . t(9;14)(p13;q32). Atlas Genet Cytogenet Oncol Haematol. October 2002 . URL : http://AtlasGeneticsOncology.org/Genes/t0914p13q32ID2018.html

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indexed on : Wed Sep 24 21:07:09 2008

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