dic(3;9)(p14;p13) PAX5/FOXP1

2010-08-01   Jean-Loup Huret  

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Acute lymphoblastic leukaemia (ALL).

Phenotype stem cell origin

B-cell precursor ALL.

Epidemiology

One case to date (Mullighan et al., 2007).

Prognosis

No data.

Genes Involved and Proteins

Gene name
PAX5 (paired box gene 5)
Location
9p13.2
Protein description
Lineage-specific transcription factor; recognizes the concensus recognition sequence GNCCANTGAAGCGTGAC, where N is any nucleotide. Involved in B-cell differentiation. Entry of common lymphoid progenitors into the B cell lineage depends on E2A, EBF1, and PAX5; activates B-cell specific genes and repress genes involved in other lineage commitments. Activates the surface cell receptor CD19 and repress FLT3. Pax5 physically interacts with the RAG1/RAG2 complex, and removes the inhibitory signal of the lysine-9-methylated histone H3, and induces V-to-DJ rearrangements. Genes repressed by PAX5 expression in early B cells are restored in their function in mature B cells and plasma cells, and PAX5 repressed (Fuxa et al., 2004; Johnson et al., 2004; Zhang et al., 2006; Cobaleda et al., 2007).
Gene name
FOXP1 (Forkhead box P1)
Location
3p13
Protein description
Transcriptional repressor. Involved in cardiomyocyte proliferation, motor neuron migration, B-lymphocyte development, and the generation of quiescent naive T cells (Shi et al., 2008; Feng et al., 2010; Rao et al., 2010; Zhang et al., 2010; Hisaoka et al., 2010).

Result of the Chromosomal Anomaly

Description

Fusion of PAX5 exon 6 to FOXP1 exon 7.
Atlas Image

Description

The predicted fusion protein contains the DNA binding paired domain of PAX5 and the DNA-binding and transcriptional regulator domain of FOXP1. 877 amino acids.

Highly cited references

Pubmed IDYearTitleCitations
282199272017Molecular role of the PAX5-ETV6 oncoprotein in promoting B-cell acute lymphoblastic leukemia.16
219628972011FOXP1 and PAX5 are rare but recurrent translocations partners in acute lymphoblastic leukemia.2

Article Bibliography

Pubmed IDLast YearTitleAuthors
174404522007Pax5: the guardian of B cell identity and function.Cobaleda C et al
199656542010Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development.Feng X et al
150040082004Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.Fuxa M et al
200403672010The forkhead transcription factors, Foxp1 and Foxp2, identify different subpopulations of projection neurons in the mouse cerebral cortex.Hisaoka T et al
152585792004B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.Johnson K et al
173448592007Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.Mullighan CG et al
205985882010MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1.Rao DS et al
187997272008Down-regulation of the forkhead transcription factor Foxp1 is required for monocyte differentiation and macrophage function.Shi C et al
207135182010Foxp1 coordinates cardiomyocyte proliferation through both cell-autonomous and nonautonomous mechanisms.Zhang Y et al
166801442006Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.Zhang Z et al

Summary

Fusion gene

PAX5/FOXP1 PAX5 (9p13.2) FOXP1 (3p13) M t(3;9)(p13;p13)|PAX5/FOXP1 PAX5 (9p13.2) FOXP1 (3p13) TIC

Note

u0007NOTE See also the paper on dic(9;20)(p11-13;q11).

Citation

Jean-Loup Huret

dic(3;9)(p14;p13) PAX5/FOXP1

Atlas Genet Cytogenet Oncol Haematol. 2010-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1553/gene-fusions-explorer/js/lib/hgnc