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t(9;13)(p12;q21) PAX5::DACH1

Written2014-01Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1560

Clinics and Pathology

Disease B-cell acute lymphoblastic leukemia (B-ALL)
Epidemiology Only one case to date, a 5-year old boy with a CD10+ ALL (Nebral et al., 2009).
Prognosis The patient was noted at an intermediate risk, reached complete remission, and was alive at 23 months+.

Genes involved and Proteins

Gene NamePAX5 (paired box gene 5)
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 NameDACH1 (dachshund family transcription factor 1)
Location 13q21.33
Dna / Rna 2 splice transcript variants.
Protein 708 and 760 amino acids (aa). From N-term to C-term (for the 760 aa form), contains a Poly-Ala (aa 61-68), three Poly-Gly (aa 74-89; aa 92-103; aa 116-123), a Poly-Ser (aa 142-165), a Dachshund domain motif N (aa 191-277), an interaction region with SIX6 (14q23.1) and HDAC3 (5q31) (aa 191-386), two Poly-Ala (aa 327-335; aa 469-472), a Dachshund Domain motif C (aa 618-698), an interaction region with SIN3A (15q24.2) and SIN3B (19p13.11),(aa 629-708), and a Coiled coil domain (aa 632-720) (Swiss-Prot).
DACH1 is a tumor suppressor. DACH1 downregulates EGFR (7p11.2), CCND1 (11q13), ESR1 (6q25.1) and AR (Xq12), and also TGFB1 (19q13.2), through interaction with SMAD4 (18q21.2) and NCOR1 (17p11.2). DACH1 coprecipitates the histone deacetylase proteins (HDAC1, HDAC2, and NCOR1). DACH1 transcriptionally represses JUN (1p32.1), and FOS (14q24.3), and DACH1 inhibits DNA synthesis and cellular proliferation (Wu et al., 2007). DACH1 is involved in the PAX-EYA-SIX-DACH regulatory pathway (eyeless (PAX6), sine oculis (SIX1, SIX2, SIX3, SIX4, SIX5, SIX6), eyes absent (EYA1, EYA2, EYA3, EYA4), and dachshund (DACH1-2)). CREBBP (16p13.3) is involved in this process.
DACH1 is involved in the development of the neocortex and the hippocampus, is expressed by neural stem cells during early neurogenesis, and also in adult neurogenesis following brain ischemia (Honsa et al., 2013). DACH1 inhibits breast cancer cellular proliferation via cyclin D1 (Nan et al., 2009). DACH1 suppresses epithelial-mesenchymal transition via repression of cytoplasmic translational induction of SNAI2 (8q11.21) by inactivating YBX1 (1p34.2). DACH1 blockes YBX1-induced mammary tumor growth (Wu et al., 2014). DACH1 expression appears to be predictive of good prognosis in oestrogen receptor (ER) positive breast cancer (Powe et al., 2014). DACH1 inhibites prostate cancer cellular DNA synthesis and growth (Wu et al., 2009). DACH1, BMP7 (20q13.31), and MECOM (EVI1, 3q26.2) were up-regulated in advanced-stage ovarian cancers, and inhibited TGF-beta signaling in these cancers associated with TGFb resistance (Purcell et al., 2005). DACH1 is frequently methylated in hepatocellular carcinoma and DACH1 expression is regulated by promoter hypermethylation. Down-regulation of DACH1 is a novel mechanism for gaining resistance to the TGFB1 (19q13.2) antiproliferative signaling (Zhu et al., 2013). DACH1 is also frequently methylated in human colorectal cancer and methylation of DACH1 may serve as detective and prognostic marker in colorectal cancer (Yan et al., 2013). DACH1 regulates FGF2 (4q27)-mediated tumor-initiating activity of glioma cells and inhibits formation of tumor-initiating spheroids of glioma cells (Watanabe et al., 2011).

Result of the chromosomal anomaly

Hybrid gene
Description Fusion of PAX5 exon 5 to DACH1 exon 5.
Fusion Protein
  PAX5/DACH1 fusion protein.
Description 585 amino acids. The predicted fusion protein contains the DNA binding paired domain of PAX5 (the 201 N-term aa) and the DACHbox-C of DACH1 (the 384 C-term aa).

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.


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
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
Focal cerebral ischemia induces the neurogenic potential of mouse Dach1-expressing cells in the dorsal part of the lateral ventricles.
Honsa P, Pivonkova H, Anderova M.
Neuroscience. 2013 Jun 14;240:39-53. doi: 10.1016/j.neuroscience.2013.02.048. Epub 2013 Mar 1.
PMID 23458709
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
Altered expression of DACH1 and cyclin D1 in endometrial cancer.
Nan F, Lu Q, Zhou J, Cheng L, Popov VM, Wei S, Kong B, Pestell RG, Lisanti MP, Jiang J, Wang C.
Cancer Biol Ther. 2009 Aug;8(16):1534-9. Epub 2009 Aug 8.
PMID 19502783
Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia.
Nebral K, Denk D, Attarbaschi A, Konig M, Mann G, Haas OA, Strehl S.
Leukemia. 2009 Jan;23(1):134-43. doi: 10.1038/leu.2008.306. Epub 2008 Nov 20.
PMID 19020546
The Dachshund gene in development and hormone-responsive tumorigenesis.
Popov VM, Wu K, Zhou J, Powell MJ, Mardon G, Wang C, Pestell RG.
Trends Endocrinol Metab. 2010 Jan;21(1):41-9. doi: 10.1016/j.tem.2009.08.002. Epub 2009 Nov 5. (REVIEW)
PMID 19896866
DACH1: its role as a classifier of long term good prognosis in luminal breast cancer.
Powe DG, Dhondalay GK, Lemetre C, Allen T, Habashy HO, Ellis IO, Rees R, Ball GR.
PLoS One. 2014 Jan 2;9(1):e84428. doi: 10.1371/journal.pone.0084428. eCollection 2014.
PMID 24392136
Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction.
Purcell P, Oliver G, Mardon G, Donner AL, Maas RL.
Gene Expr Patterns. 2005 Dec;6(1):110-8. Epub 2005 Jul 18.
PMID 16024294
Homozygously deleted gene DACH1 regulates tumor-initiating activity of glioma cells.
Watanabe A, Ogiwara H, Ehata S, Mukasa A, Ishikawa S, Maeda D, Ueki K, Ino Y, Todo T, Yamada Y, Fukayama M, Saito N, Miyazono K, Aburatani H.
Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12384-9. doi: 10.1073/pnas.0906930108. Epub 2011 Jul 12.
PMID 21750150
Cell fate factor DACH1 represses YB-1-mediated oncogenic transcription and translation.
Wu K, Chen K, Wang C, Jiao X, Wang L, Zhou J, Wang J, Li Z, Addya S, Sorensen PH, Lisanti MP, Quong A, Ertel A, Pestell RG.
Cancer Res. 2014 Feb 1;74(3):829-39. doi: 10.1158/0008-5472.CAN-13-2466. Epub 2013 Dec 12.
PMID 24335958
The cell fate determination factor dachshund inhibits androgen receptor signaling and prostate cancer cellular growth.
Wu K, Katiyar S, Witkiewicz A, Li A, McCue P, Song LN, Tian L, Jin M, Pestell RG.
Cancer Res. 2009 Apr 15;69(8):3347-55. doi: 10.1158/0008-5472.CAN-08-3821. Epub 2009 Apr 7.
PMID 19351840
Cell fate determination factor DACH1 inhibits c-Jun-induced contact-independent growth.
Wu K, Liu M, Li A, Donninger H, Rao M, Jiao X, Lisanti MP, Cvekl A, Birrer M, Pestell RG.
Mol Biol Cell. 2007 Mar;18(3):755-67. Epub 2006 Dec 20.
PMID 17182846
Epigenetic regulation of DACH1, a novel Wnt signaling component in colorectal cancer.
Yan W, Wu K, Herman JG, Brock MV, Fuks F, Yang L, Zhu H, Li Y, Yang Y, Guo M.
Epigenetics. 2013 Dec;8(12):1373-83. doi: 10.4161/epi.26781. Epub 2013 Oct 22.
PMID 24149323
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
Epigenetic silencing of DACH1 induces loss of transforming growth factor-b1 antiproliferative response in human hepatocellular carcinoma.
Zhu H, Wu K, Yan W, Hu L, Yuan J, Dong Y, Li Y, Jing K, Yang Y, Guo M.
Hepatology. 2013 Dec;58(6):2012-22. doi: 10.1002/hep.26587. Epub 2013 Oct 21.
PMID 23787902


This paper should be referenced as such :
Huret, JL
t(9;13)(p12;q21) PAX5/DACH1
Atlas Genet Cytogenet Oncol Haematol. 2014;18(8):605-607.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Translocations implicated (Data extracted from papers in the Atlas)

 t(9;13)(p12;q21) PAX5/DACH1

External links

PAX5 (9p13.2) DACH1 (13q21.33)

PAX5 (9p13.2) DACH1 (13q21.33)

Mitelman databaset(9;13)(p12;q21)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databasePAX5::DACH1 [MCList]  PAX5 (9p13.2) DACH1 (13q21.33)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 16:37:02 CEST 2021

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