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t(1;19)(q22;p13.2) MEF2D/DAZAP1

Written2019-05Tatiana Gindina
R.M. Gorbacheva Memorial Institute of Children Oncology Hematology and Transplantation at First Pavlov Saint-Petersburg State Medical University, Saint-Petersburg, Russia / tatgindina@gmail.com

Abstract Review on t(1;19)(q22;p13.2) MEF2D/DAZAP1, with data on the genes involved

Keywords Chromosome 1 ; Chromosome 19 ; t(1;19)(q22;p13.3) ; MEF2D ; DAZAP1 ;

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1843

Clinics and Pathology

Disease B lymphoblastic leukemia
Epidemiology Only one case to date: a 3-year-old female child (Yuki et al., 2004; Prima et al., 2005; Liu et al., 2016).

Cytogenetics

Note The cells carry t(1;19) but lack TCF3 (E2A) rearrangements and do not express E2A/ PBX1.

Genes involved and Proteins

Gene NameMEF2D (Myocyte Enhancer Factor 2D)
Location 1q22
Protein MEF2D belongs to the MADS-box family of transcription factors; this molecule binds as a homo- or hetero-dimer to the MEF2 element present in the regulatory regions of numerous muscle-specific and growth-factor and stress-induced genes. A remarkable increase in expression levels of MEF2A and MEF2D has been reported during differentiation into monocytes using the promyeloid HL-60 cell line (Yuki et al., 2004). In mouse models, MEF2D was identified as a candidate oncogene involved in the pathogenesis of leukemia. It is assumed, that native MEF2D has latent transforming properties, which can be unmasked via aberrant protein expression (Prima et al., 2005).
Gene NameDAZAP1 (Deleted in Azoospermia-Associated Protein 1)
Location 19p13.3
Protein DAZAP1 is an RNA binding protein, which contains two RNA-recognition motifs (RRMs), a proline-rich C-terminal portion and expressed most abundantly in the testis during spermatogenesis, and to a lower level, in the thymus.

Result of the chromosomal anomaly

Hybrid gene
Description The genes were fused in-frame between exon 6 of MEF2D and exon 7 of DAZAP1 (MEF2D/DAZAP1), as well as, between exon 6 of DAZAP1 and exon 7 of MEF2D (DAZAP1/MEF2D). Sequencing of the RT-PCR products confirmed in-frame fusions between MEF2D (codon 222) and DAZAP1 (codon 155) in both chimeric transcripts (Yuki et al., 2004).
Transcript Both chimeric transcripts, MEF2D/DAZAP1 and DAZAP1/MEF2D, whose sequences indicated in-frame fusions between MEF2D and DAZAP1 were expressed in bone marrow cells (Yuki et al., 2004).
  
Fusion Protein
 
  Schematic representation of the wild-type MEF2D and DAZAP1 products and of the chimeric fusion proteins MEF2D/DAZAP1 and DAZAP1/MEF2D.
Expression Localisation MEF2D/DAZAP1 and DAZAP1/MEF2D proteins were both located in the nucleus, MEF2D/DAZAP1 was able to form dimers with MEF2D and HDAC4. Furthermore, exogenous expression of MEF2D/DAZAP1 and DAZAP1/MEF2D promoted the growth of HeLa cells (Yuki et al., 2004).
Oncogenesis MEF2D/DAZAP1 and/or DAZAP1/MEF2D contribute to leukemogenesis by altering signaling pathways normally regulated by wild-type MEF2D and DAZAP1. MEF2D/DAZAP1 binds avidly and specifically to DNA and is a substantially more potent transcriptional activator, than MEF2D and also may associate more strongly with other proteins involved in transcriptional regulation (e.g. HDAC4). MEF2D/DAZAP1 might immediately activate transcription of genes crucial for lymphocyte growth and/or survival such as IL2 (interleukin-2), a known transcriptional target of MEF2D in T-cells. As well, MEF2D/DAZAP1 could contribute to leukemogenesis via dysregulated activation of MAPK-mediated cell proliferation pathways. These alterations may confer more potent transforming properties to MEF2D/DAZAP1, which can be further augmented by coexpression with the reciprocal DAZAP1/MEF2D chimera, which retains sequence-specific RNA binding properties (Prima et al., 2005).
  

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

Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia
Liu YF, Wang BY, Zhang WN, Huang JY, Li BS, Zhang M, Jiang L, Li JF, Wang MJ, Dai YJ, Zhang ZG, Wang Q, Kong J, Chen B, Zhu YM, Weng XQ, Shen ZX, Li JM, Wang J, Yan XJ, Li Y, Liang YM, Liu L, Chen XQ, Zhang WG, Yan JS, Hu JD, Shen SH, Chen J, Gu LJ, Pei D, Li Y, Wu G, Zhou X, Ren RB, Cheng C, Yang JJ, Wang KK, Wang SY, Zhang J, Mi JQ, Pui CH, Tang JY, Chen Z, Chen SJ
EBioMedicine 2016 Jun;8:173-183
PMID 27428428
 
Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13
Prima V, Gore L, Caires A, Boomer T, Yoshinari M, Imaizumi M, Varella-Garcia M, Hunger SP
3) in acute lymphoblastic leukemia Leukemia
PMID 15744350
 
Identification of a novel fusion gene in a pre-B acute lymphoblastic leukemia with t(1;19)(q23;p13)
Yuki Y, Imoto I, Imaizumi M, Hibi S, Kaneko Y, Amagasa T, Inazawa J
Cancer Sci 2004 Jun;95(6):503-7
PMID 15182431
 

Citation

This paper should be referenced as such :
Gindina T
t(1;19)(q22;p13.2) MEF2D/DAZAP1;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0119MEF2DDAZAP1ID1843.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(1;19)(q22;p13) MEF2D/DAZAP1

External links

Mitelman databaset(1;19)(q22;p13) [Case List]    t(1;19)(q22;p13) [Transloc-MCList] MEF2D/DAZAP1 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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