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t(5;11)(q33;q13) NUMA1/PDGFRB a novel fusion

Written2017-03Ibrahima Ba, Virginie Eclache, Emmanuelle Clappier
Hematology Laboratory, APHP, Hôpital Saint-Louis, Paris, France; Hematology Laboratory, APHP, Hôpital Avicenne, Bobigny, France; ibrahima.ba@aphp.fr; virginie.eclache@aphp.fr; emmanuelle.clappier@aphp.fr

Abstract A novel NUMA1/PDGFRB fusion identified in B-cell precursor acute lymphoblastic leukemia is described.

Keywords Chromosome 5; chromosome 11; acute lymphoblastic leukemia; B-ALL; NUMA1; PDGFRB; translocation t(5;11)(q33;q13); fusion gene

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9820/3
Atlas_Id 1693
 
  t(5;11)(q33;q13) R-banding, courtesy Virginie Eclache.

Clinics and Pathology

Disease B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
Phenotype / cell stem origin Common-B immunophenotype (B-II EGIL classification): CD19+, CD22+, CD79a+, CD10+, Cμ -
Epidemiology Only one case described, a 61-year-old man.
Treatment GRAAL 2012 (Group for Research in Adult Acute Lymphoblastic Leukemia).

Cytogenetics

Cytogenetics Morphological Unbalanced t(5;11): t(5;11)(q33;q13),+der(5)t(5;11).
 
  CGH analysis suggested a rearrangement between 5q33 and 11q13.

Genes involved and Proteins

Gene Name PDGFRB
Location 5q32
Dna / Rna PDGFRB locus spans approximately 149.5 Mb and contains 23 exons. PDGFRB has been involved in over 30 gene fusion (Roberts, 2012; Kobayashi, 2014).
Protein The PDGRFB gene encodes a protein of 1106 amino acids with a molecular weight of approximately 124 kDa. Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Play an essential role in blood vessel development by promoting proliferation, migration and recruitment of pericytes and smooth muscle cells to endothelial cells. Binding of its cognate ligands - homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFD - leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB.
Gene Name NUMA1
Location 11q13.4
Dna / Rna NUMA1 locus spans approximately 78 kb and contains 27 exons.; NUMA1 has been involved in a gene fusion with RARA (Wells RA, 1997; Melnick, 1999)
Protein The NUMA1 gene encodes a protein of 2115 amino acids with a molecular weight of approximately 230 kDa. Highly abundant component of the nuclear matrix where it may serve a non-mitotic structural role, occupies the majority of the nuclear volume. Required for maintenance and establishment of the mitotic spindle poles, functioning as a tether linking bulk microtubules of the spindle to centrosomes. May be involved in coordination of the alignment of the mitotic spindle to the cellular polarity axis, which is a prerequisite for asymmetric cell divisions (Silk, 2009).

Result of the chromosomal anomaly

Hybrid gene
  The cDNA sequence analysis identified an in frame transcript fusing exon 22 of NUMA1 with exon 10 of PDGFRB
 
Description 5' NUTM1 - 3' PDGFRB. NUMA1 exon 22 is fused in frame with PDGFRB exon 11.
Transcript The NUMA1-PDGFRB fusion transcript was amplified.
  
Fusion Protein
 
  NUTM1/PDGFRB fusion protein.
  

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

Requirements for NuMA in maintenance and establishment of mammalian spindle poles
Alain D. Silk, Andrew J. Holland and Don W. Cleveland
J Cell Biol. 2009 ; 184(5): 677-690
PMID 19255246
 
ATF7IP as a novel PDGFRB fusion partner in acute lymphoblastic leukaemia in children
Kobayashi K, Mitsui K & Ohara A
Br J Haematol. 2014 ; 165(6):836-41
PMID 24628626
 
Deconstructing a Disease: RARA, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia
Melnick A & Licht JD
Blood 1999 ; 93(10):3167-215
PMID 10233871
 
Fusion of retinoic acid receptor ? to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia
Richard A. Wells, Charles Catzavelos & Suzanne Kamel-Reid
Nature Genetics 1997 ; 17(1):109-13
PMID 21330321
 
Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia
Roberts KG, Morin RD & Mullighan CG
Cancer Cell 2012 ; 14;22(2):153-66
PMID 22897847
 

Citation

This paper should be referenced as such :
Ba I, Eclache V, Clappier E
t(5;11)(q33;q13) NUMA1/PDGFRB a novel fusion;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0511q33q13ID1693.html


Translocations implicated (Data extracted from papers in the Atlas)

 t(5;11)(q33;q13) NUMA1/PDGFRB

External links

Mitelman databaset(5;11)(q33;q13) [Case List]    t(5;11)(q33;q13) [Association List] Mitelman database (CGAP - NCBI)
arrayMapMorph ( 9820/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaset(5;11)(q33;q13) NUMA1/PDGFRB a novel fusion
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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