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t(7;9)(q11.2;p13.2) PAX5::AUTS2

Written2013-11Dagmar Denk
CCRI, Children's Cancer Research Institute, St. Anna Kinderkrebsforschung e.V., Zimmermannplatz 10, 1090 Vienna, Austria

(Note : for Links provided by Atlas : click)


ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1633

Clinics and Pathology

Disease B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
Epidemiology This unbalanced chromosomal rearrangement was found in three pediatric patients with B-cell precursor acute lymphoblastic leukemia (Kawamata et al., 2008; Coyaud et al., 2010a; Denk et al., 2012).
Clinics All three patients achieved a complete remission (CR) after completion of induction therapy; however, two of the patients experienced an early relapse and both patients died, one from an infectious complication in second CR and one from progressive leukemia after a further relapse. The third patient remains in first CR for more than two years after diagnosis (Denk et al., 2012).

Genes involved and Proteins

Gene NamePAX5 (paired box gene 5)
Location 9p13.2
Dna / Rna 10 exons, alternatively spliced transcript variants encoding different isoforms.
Protein PAX5 is a transcription factor harboring a conserved paired box DNA-binding domain. It is a master regulator of B-cell commitment and maintenance and within the hematopoietic system is expressed in B-cells from the pro-B cell to the mature B-cell stage and repressed upon plasma cell differentiation (Cobaleda et al., 2007; Medvedovic et al., 2011). In BCP-ALL PAX5 is a frequent target of somatic mutations, comprising deletions, point mutations, and structural rearrangements resulting in the expression of fusion transcripts (Mullighan et al., 2007). To date, 16 different in-frame PAX5 fusions genes have been reported in B-ALL (Cazzaniga et al., 2001; Bousquet et al., 2007; Mullighan et al., 2007; Nebral et al., 2007; Kawamata et al., 2008; Nebral et al., 2009; Coyaud et al., 2010b; Lee et al., 2012). The PAX5 fusion partners comprise a heterogeneous group of genes that encode transcription factors, structural proteins, kinases, as well as several genes with so far unknown functions.
Gene NameAUTS2 (autism susceptibility candidate 2)
Location 7q11.22
Dna / Rna 19 exons, alternatively spliced transcript variants encoding different isoforms.
Protein AUTS2, is a highly conserved nuclear protein with so far unknown function, contains several putative N-terminal nuclear localization signals (NLS), two proline alternating with two histidine-rich regions, and two potential serine phosphorylation sites. It is strongly expressed in fetal and adult brain, particularly in the frontal, parietal, and temporal lobes. Mutations in the gene have been associated with autism and mental retardation (Oksenberg and Ahituv, 2013).

Result of the chromosomal anomaly

Hybrid gene
Transcript In-frame fusions between PAX5 exon 6 and AUTS2 exon 4, 5 or 6 have been described (Kawamata et al., 2008; Coyaud et al., 2010; Denk et al., 2012).
Fusion Protein
  Figure 1. Schematic representation of the structure of AUTS2 (top) and PAX5 (bottom) wild-type proteins as well as the putative consensus chimeric protein (middle). PD: paired domain; OP: octapeptide; HD: partial homeodomain; TA: transactivation domain; I: inhibitory domain; H: histidine-rich regions; P: proline-rich region; arrows indicate nuclear localization signals (NLS); filled lollipops represent serine phosphorylation sites.
Description The putative consensus chimeric protein contains the DNA-binding paired domain, the octapeptide, and the partial homeodomain of PAX5 fused to the C-terminal regions of AUTS2.

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.


A novel PAX5-ELN fusion protein identified in B-cell acute lymphoblastic leukemia acts as a dominant negative on wild-type PAX5.
Bousquet M, Broccardo C, Quelen C, Meggetto F, Kuhlein E, Delsol G, Dastugue N, Brousset P.
Blood. 2007 Apr 15;109(8):3417-23. Epub 2006 Dec 19.
PMID 17179230
The paired box domain gene PAX5 is fused to ETV6/TEL in an acute lymphoblastic leukemia case.
Cazzaniga G, Daniotti M, Tosi S, Giudici G, Aloisi A, Pogliani E, Kearney L, Biondi A.
Cancer Res. 2001 Jun 15;61(12):4666-70.
PMID 11406533
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. 2010b Apr 15;115(15):3089-97. doi: 10.1182/blood-2009-07-234229. Epub 2010 Feb 16.
PMID 20160164
PAX5-AUTS2: a recurrent fusion gene in childhood B-cell precursor acute lymphoblastic leukemia.
Denk D, Nebral K, Bradtke J, Pass G, Moricke A, Attarbaschi A, Strehl S.
Leuk Res. 2012 Aug;36(8):e178-81. doi: 10.1016/j.leukres.2012.04.015. Epub 2012 May 12. (REVIEW)
PMID 22578776
Cloning of genes involved in chromosomal translocations by high-resolution single nucleotide polymorphism genomic microarray.
Kawamata N, Ogawa S, Zimmermann M, Niebuhr B, Stocking C, Sanada M, Hemminki K, Yamatomo G, Nannya Y, Koehler R, Flohr T, Miller CW, Harbott J, Ludwig WD, Stanulla M, Schrappe M, Bartram CR, Koeffler HP.
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11921-6. doi: 10.1073/pnas.0711039105. Epub 2008 Aug 12.
PMID 18697940
Sequential array comparative genomic hybridization analysis identifies copy number changes during blastic transformation of chronic myeloid leukemia.
Lee ST, Ji Y, Kim HJ, Ki CS, Jung CW, Kim JW, Kim SH.
Leuk Res. 2012 Apr;36(4):418-21. doi: 10.1016/j.leukres.2011.12.021. Epub 2012 Feb 5.
PMID 22309891
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
Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia.
Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui CH, Relling MV, Evans WE, Shurtleff SA, Downing JR.
Nature. 2007 Apr 12;446(7137):758-64.
PMID 17344859
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
Identification of PML as novel PAX5 fusion partner in childhood acute lymphoblastic leukaemia.
Nebral K, Konig M, Harder L, Siebert R, Haas OA, Strehl S.
Br J Haematol. 2007 Oct;139(2):269-74.
PMID 17897302
The role of AUTS2 in neurodevelopment and human evolution.
Oksenberg N, Ahituv N.
Trends Genet. 2013 Oct;29(10):600-8. doi: 10.1016/j.tig.2013.08.001. Epub 2013 Sep 2.
PMID 24008202


This paper should be referenced as such :
Denk, D
t(7;9)(q11.2;p13.2) PAX5/AUTS2
Atlas Genet Cytogenet Oncol Haematol. 2014;18(6):434-435.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes AUTS2

Translocations implicated (Data extracted from papers in the Atlas)

 t(7;9)(q11.2;p13.2) PAX5/AUTS2

External links

PAX5 (9p13.2) AUTS2 (7q11.22)

PAX5 (9p13.2) AUTS2 (7q11.22)

Mitelman databaset(7;9)(q11.2;p13.2)
arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databasePAX5::AUTS2 [MCList]  PAX5 (9p13.2) AUTS2 (7q11.22)
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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