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dic(9;18)(p13;q11) PAX5/ZNF521

Written2010-08Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1556
Note NOTE See also the paper on dic(9;20)(p11-13;q11).

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.

Genes involved and Proteins

Gene Name PAX5
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 ZNF521
Location 18q11
Protein Transcription factor. Involved in B-cell lineage commitment, in the differentiation of neural progenitors; Inhibits EBF1. Binds Runx2 and represses its transcriptional activity. Regulates osteoblast differentiation and bone formation (Bond et al., 2008; Lobo et al., 2008; Wu et al., 2009; Hesse et al., 2010).

Result of the chromosomal anomaly

Hybrid gene
Description Fusion of PAX5 exon 7 to ZNF521 exon 4.
  
Fusion Protein
 
Description The predicted fusion protein contains the DNA binding paired domain of PAX5 and the DNA-binding and transcriptional regulator domain of ZNF521. 1541 amino acids.
  

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

Early hematopoietic zinc finger protein-zinc finger protein 521: a candidate regulator of diverse immature cells.
Bond HM, Mesuraca M, Amodio N, Mega T, Agosti V, Fanello D, Pelaggi D, Bullinger L, Grieco M, Moore MA, Venuta S, Morrone G.
Int J Biochem Cell Biol. 2008;40(5):848-54. Epub 2007 Apr 21.
PMID 17543573
 
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
 
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
 
Zinc finger protein 521, a new player in bone formation.
Hesse E, Kiviranta R, Wu M, Saito H, Yamana K, Correa D, Atfi A, Baron R.
Ann N Y Acad Sci. 2010 Mar;1192(1):32-7.
PMID 20392215
 
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
 
Pivotal role of early B-cell factor 1 in development of striatonigral medium spiny neurons in the matrix compartment.
Lobo MK, Yeh C, Yang XW.
J Neurosci Res. 2008 Aug 1;86(10):2134-46.
PMID 18338816
 
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
 
Zfp521 antagonizes Runx2, delays osteoblast differentiation in vitro, and promotes bone formation in vivo.
Wu M, Hesse E, Morvan F, Zhang JP, Correa D, Rowe GC, Kiviranta R, Neff L, Philbrick WM, Horne WC, Baron R.
Bone. 2009 Apr;44(4):528-36. Epub 2008 Nov 27.
PMID 19095088
 
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
 

Citation

This paper should be referenced as such :
Huret, JL
dic(9;18)(p13;q11) PAX5/ZNF521
Atlas Genet Cytogenet Oncol Haematol. 2011;15(5):465-466.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/dic0918p13q11ID1556.html


Translocations implicated (Data extracted from papers in the Atlas)

 dic(9;18)(p13;q11) PAX5/ZNF521

External links

PAX5 (9p13.2) ZNF521 (18q11.2)

PAX5 (9p13.2) ZNF521 (18q11.2)

Mitelman databasedic(9;18)(p13;q11) [Case List]    dic(9;18)(p13;q11) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databasePAX5/ZNF521 [MCList]  PAX5 (9p13.2) ZNF521 (18q11.2)
TICdbPAX5/ZNF521  PAX5 (9p13.2) ZNF521 (18q11.2)
 
Disease databasedic(9;18)(p13;q11) PAX5/ZNF521
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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