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dic(9;17)(p13;q11) PAX5/TAOK1

Written2014-04Jean-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 1598

Clinics and Pathology

Disease Acute lymphoblastic leukemia (ALL)
Epidemiology Only one case to date, a 3-year old girl with a pre-B-ALL (Coyaud et al., 2010).

Cytogenetics

Additional anomalies There was a +X and additional rearrangements.

Genes involved and Proteins

Gene Name PAX5
Location 9p13.2
Protein 391 amino acids; from N-term to C-term, PAX5 contains: a paired domain (aa: 16-142); an octapeptide (aa: 179-186); a partial homeodomain (aa: 228-254); a transactivation domain (aa: 304-359); and an inhibitory domain (aa: 359-391). 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; Medvedovic et al., 2011).
Gene Name TAOK1
Location 17q11.2
Protein 1001 amino acids (aa); from N-term to C-term, TAOK1 contains: a protein kinase domain (aa 28-281), a nucleotide binding site (aa 34-42), a poly-Glu stretch (aa 330-334), a Ser-rich region (aa 347-379), and coiled coil domains (aa 458-651; 754-877). Phosphorylation on Ser/Thr followed by Gln are the following: SQ motifs: aa 363-364; 554-555; 990-991, TQ motifs: aa 502-503; 643-644; 785-786 (Raman et al., 2007).
TAOK1 is a serine/threonine-protein kinase. TAOK1 has the ability to phosphorylate MARK1 (MAP/Microtubule affinity-regulating kinase 1, 1q41), a kinase regulating microtubule dynamics and cell polarity (Timm et al., 2003). TAOK1 regulates apoptotic morphology via C-Jun N-terminal kinases (MAPK8, 10q11.22; MAPK9, 5q35.3; MAPK10, 4q21.3) and ROCK1 (Rho-associated, coiled-coil containing protein kinase 1, 18q11.1) (Zihni et al., 2006). TAOK1 alters actin cytoskeletal organization and binds to microtubules, regulating their organization and stability (Zihni et al., 2006). The TAO kinases (TAOK1; TAOK2, 16p11.2; TAOK3, 12q24.23) mediate the activation of p38 (MAPK11, 22q13.33; MAPK12, 22q13.33; MAPK13, 6p21.31; MAPK14, 6p21.31) in response to various genotoxic stimuli. ATM (ataxia telangiectasia mutated, 11q22.3) phosphorylates the TAO kinases. TAO kinases are regulators of p38-mediated responses to DNA damage and are intermediates in the activation of p38 by ATM (Hutchison et al., 1998; Raman et al., 2007). TESK1 (testis-specific kinase 1, 9p13.3) binds to and inhibits TAOK1. The elevation of TAOK1 results in microtubule disruption. SPRED1 (sprouty-related, EVH1 domain containing 1, 15q14) - TESK1 binding causes inhibition of TESK1, making F-actin fibers dynamic (Johne et al., 2008). Taok1 controls epithelial morphogenesis by promoting Fas2 (Fasciclin 2, the insect homologue of NCAM1 (neural cell adhesion molecule 1, 11q23.2)) endocytosis in Drosophila melanogaster (Gomez et al., 2012).

Result of the chromosomal anomaly

Hybrid gene
Description Fusion of PAX5 exon 5 to TAOK1 intron 19-20, but in reverse orientation. Transcript with exon 1B to exon 5 of PAX5, and an additional sequence of 54 bp.
  
Fusion Protein
 
  PAX5-TAOK1 translocation protein.
Description Predicted fusion protein of 218 amino acids. The predicted fusion protein contains the DNA binding paired domain of PAX5 (201 aa) and 17 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

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. (REVIEW)
PMID 17440452
 
Wide diversity of PAX5 alterations in B-ALL: a Groupe Francophone de Cytogenetique Hematologique study.
Coyaud E, Struski S, Prade N, Familiades J, Eichner R, Quelen C, Bousquet M, Mugneret F, Talmant P, Pages MP, Lefebvre C, Penther D, Lippert E, Nadal N, Taviaux S, Poppe B, Luquet I, Baranger L, Eclache V, Radford I, Barin C, Mozziconacci MJ, Lafage-Pochitaloff M, Antoine-Poirel H, Charrin C, Perot C, Terre C, Brousset P, Dastugue N, Broccardo C.
Blood. 2010 Apr 15;115(15):3089-97. doi: 10.1182/blood-2009-07-234229. Epub 2010 Feb 16.
PMID 20160164
 
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
 
Tao controls epithelial morphogenesis by promoting Fasciclin 2 endocytosis.
Gomez JM, Wang Y, Riechmann V.
J Cell Biol. 2012 Dec 24;199(7):1131-43. doi: 10.1083/jcb.201207150.
PMID 23266957
 
Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades.
Hutchison M, Berman KS, Cobb MH.
J Biol Chem. 1998 Oct 30;273(44):28625-32.
PMID 9786855
 
Spred1 and TESK1--two new interaction partners of the kinase MARKK/TAO1 that link the microtubule and actin cytoskeleton.
Johne C, Matenia D, Li XY, Timm T, Balusamy K, Mandelkow EM.
Mol Biol Cell. 2008 Apr;19(4):1391-403. doi: 10.1091/mbc.E07-07-0730. Epub 2008 Jan 23.
PMID 18216281
 
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
 
Pax5: a master regulator of B cell development and leukemogenesis.
Medvedovic J, Ebert A, Tagoh H, Busslinger M.
Adv Immunol. 2011;111:179-206. doi: 10.1016/B978-0-12-385991-4.00005-2. (REVIEW)
PMID 21970955
 
TAO kinases mediate activation of p38 in response to DNA damage.
Raman M, Earnest S, Zhang K, Zhao Y, Cobb MH.
EMBO J. 2007 Apr 18;26(8):2005-14. Epub 2007 Mar 29.
PMID 17396146
 
MARKK, a Ste20-like kinase, activates the polarity-inducing kinase MARK/PAR-1.
Timm T, Li XY, Biernat J, Jiao J, Mandelkow E, Vandekerckhove J, Mandelkow EM.
EMBO J. 2003 Oct 1;22(19):5090-101.
PMID 14517247
 
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
 
Prostate-derived sterile 20-like kinase 2 (PSK2) regulates apoptotic morphology via C-Jun N-terminal kinase and Rho kinase-1.
Zihni C, Mitsopoulos C, Tavares IA, Ridley AJ, Morris JD.
J Biol Chem. 2006 Mar 17;281(11):7317-23. Epub 2006 Jan 2.
PMID 16407310
 

Citation

This paper should be referenced as such :
JL Huret
dic(9;17)(p13;q11) PAX5/TAOK1
Atlas Genet Cytogenet Oncol Haematol. 2014;18(12):947-949.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/dic0917p13q11ID1598.html


Translocations implicated (Data extracted from papers in the Atlas)

 dic(9;17)(p13;q11) PAX5/TAOK1

External links

PAX5 (9p13.2) TAOK1 (17q11.2)

Mitelman databasedic(9;17)(p13;q11) [Case List]    dic(9;17)(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/TAOK1 [MCList]  PAX5 (9p13.2) TAOK1 (17q11.2)
 
Disease databasedic(9;17)(p13;q11) PAX5/TAOK1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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indexed on : Fri Jun 30 11:22:16 CEST 2017


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