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

2010-08-01   Jean-Loup Huret 

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

Clinics and Pathology

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
ZNF521 (zinc finger protein 521)
Location
18q11.2
Protein description
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

Description

Fusion of PAX5 exon 7 to ZNF521 exon 4.
Atlas Image

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.

Bibliography

Pubmed IDLast YearTitleAuthors
175435732008Early hematopoietic zinc finger protein-zinc finger protein 521: a candidate regulator of diverse immature cells.Bond HM et al
174404522007Pax5: the guardian of B cell identity and function.Cobaleda C et al
150040082004Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene.Fuxa M et al
203922152010Zinc finger protein 521, a new player in bone formation.Hesse E et al
152585792004B cell-specific loss of histone 3 lysine 9 methylation in the V(H) locus depends on Pax5.Johnson K et al
183388162008Pivotal role of early B-cell factor 1 in development of striatonigral medium spiny neurons in the matrix compartment.Lobo MK et al
173448592007Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.Mullighan CG et al
190950882009Zfp521 antagonizes Runx2, delays osteoblast differentiation in vitro, and promotes bone formation in vivo.Wu M 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/ZNF521 PAX5 (9p13.2) ZNF521 (18q11.2) M t(9;18)(p13;q11)|PAX5/ZNF521 PAX5 (9p13.2) ZNF521 (18q11.2) TIC

Note

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

Citation

Jean-Loup Huret

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

Atlas Genet Cytogenet Oncol Haematol. 2010-08-01

Online version: http://atlasgeneticsoncology.org/haematological/1556/dic(9;18)(p13;q11)-pax5-znf521

External Links