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

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Written	2010-08	Jean-Loup Huret
		Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

1. Identity

ICD-Topo	C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho	9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id	1553
Note	NOTE See also the paper on dic(9;20)(p11-13;q11).

2. Clinics and Pathology

Disease	Acute lymphoblastic leukaemia (ALL).
Phenotype / cell stem origin	B-cell precursor ALL.
Epidemiology	One case to date (Mullighan et al., 2007).
Prognosis	No data.

3. Genes involved and Proteins

Gene Name	PAX5 (paired box gene 5)
Location	9p13.2
Protein	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	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).

4. Result of the chromosomal anomaly

Hybrid gene

Description	Fusion of PAX5 exon 6 to FOXP1 exon 7.

Fusion Protein



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.

5. 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.

6. Bibliography

Pax5: the guardian of B cell identity and function.

Cobaleda C, Schebesta A, Delogu A, Busslinger M.

Nat Immunol. 2007 May;8(5):463-70.

PMID 17440452

Foxp1 is an essential transcriptional regulator for the generation of quiescent naive T cells during thymocyte development.

Feng X, Ippolito GC, Tian L, Wiehagen K, Oh S, Sambandam A, Willen J, Bunte RM, Maika SD, Harriss JV, Caton AJ, Bhandoola A, Tucker PW, Hu H.

Blood. 2010 Jan 21;115(3):510-8. Epub 2009 Nov 12.

PMID 19965654

Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.

Fuxa M, Skok J, Souabni A, Salvagiotto G, Roldan E, Busslinger M.

Genes Dev. 2004 Feb 15;18(4):411-22.

PMID 15004008

The forkhead transcription factors, Foxp1 and Foxp2, identify different subpopulations of projection neurons in the mouse cerebral cortex.

Hisaoka T, Nakamura Y, Senba E, Morikawa Y.

Neuroscience. 2010 Mar 17;166(2):551-63. Epub 2009 Dec 28.

PMID 20040367

B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.

Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K.

Nat Immunol. 2004 Aug;5(8):853-61. Epub 2004 Jul 18.

PMID 15258579

Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.

Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui CH, Relling MV, Evans WE, Shurtleff SA, Downing JR.

Nature. 2007 Apr 12;446(7137):758-64.

PMID 17344859

MicroRNA-34a perturbs B lymphocyte development by repressing the forkhead box transcription factor Foxp1.

Rao DS, O'Connell RM, Chaudhuri AA, Garcia-Flores Y, Geiger TL, Baltimore D.

Immunity. 2010 Jul 23;33(1):48-59. Epub 2010 Jul 1.

PMID 20598588

Down-regulation of the forkhead transcription factor Foxp1 is required for monocyte differentiation and macrophage function.

Shi C, Sakuma M, Mooroka T, Liscoe A, Gao H, Croce KJ, Sharma A, Kaplan D, Greaves DR, Wang Y, Simon DI.

Blood. 2008 Dec 1;112(12):4699-711. Epub 2008 Sep 17.

PMID 18799727

Foxp1 coordinates cardiomyocyte proliferation through both cell-autonomous and nonautonomous mechanisms.

Zhang Y, Li S, Yuan L, Tian Y, Weidenfeld J, Yang J, Liu F, Chokas AL, Morrisey EE.

Genes Dev. 2010 Aug 15;24(16):1746-57.

PMID 20713518

Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes.

Zhang Z, Espinoza CR, Yu Z, Stephan R, He T, Williams GS, Burrows PD, Hagman J, Feeney AJ, Cooper MD.

Nat Immunol. 2006 Jun;7(6):616-24. Epub 2006 May 7.

PMID 16680144

7. Citation

This paper should be referenced as such :

Huret, JL

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

Atlas Genet Cytogenet Oncol Haematol. 2011;15(5):463-464.

Free journal version : [ pdf ] [ DOI ]

On line version : http://atlasgeneticsoncology.usal.es/classic/Anomalies/dic0309p14p13ID1553.html

8. Translocations implicated (Data extracted from papers in the Atlas)

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

9. External links

PAX5 (9p13.2) FOXP1 (3p13)

Mitelman database	dic(3;9)(p14;p13) [Case List] dic(3;9)(p14;p13) [Transloc-MCList] PAX5/FOXP1 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)	Topo ( C42) Morph ( 9811/3) - [auto + random 100 samples .. if exist ] [tabulated segments]

Mitelman database	PAX5/FOXP1 [MCList] PAX5 (9p13.2) FOXP1 (3p13)
TICdb	PAX5/FOXP1 PAX5 (9p13.2) FOXP1 (3p13)

REVIEW articles	automatic search in PubMed
Last year articles	automatic search in PubMed
All articles	automatic search in PubMed

indexed on : Wed Nov 28 16:16:53 CET 2018

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