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dic(9;12)(p13;p13) PAX5/ETV6

Written1997-08Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2003-06Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2004-01Sabine Strehl
CCRI, Children's Cancer Research Institute St. Anna Kinderkrebsforschung Kinderspitalgasse 6 A-1090, Vienna, Austria

(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
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
Atlas_Id 1065
 
  dic(9;12)(p13;p13) G- banding - Courtesy Jean-Luc Lai (left) and Diane H. Norback, Eric B. Johnson, Sara Morrison-Delap UW Cytogenetic Services (middle left and middle); R- banding (right) with chr 12 up side down - Jean Loup Huret; diagram and C-banding (above) - Jean Loup Huret.

Clinics and Pathology

Disease Acute lymphocytic leukemia (ALL)most often; rarely: chronic myelogenous leukemia (CML) in blast crisis, T-cell leukaemia or non Hodgkin lymphoma (NHL)
Phenotype / cell stem origin ALLs with dic(9;12) are most often L1/L2 and CD10+, at times CIg+ ALL
Epidemiology 1% of paediatric ALL; sex ratio: 2M/1F; children and young adults (>1yr, <25yrs); no infant case
Clinics moderate organomegaly; blood data: moderate WBC
Treatment bone marrow transplantation is not indicated; no high risk protocol
Prognosis complete remission is obtained in all cases; 5 yrs survival > 95%

Cytogenetics

Cytogenetics Morphological dicentric with loss of parts of 9p and 12p --> ploidy: 45 chromosomes
Additional anomalies +8, +21, ...

Genes involved and Proteins

Gene Name PAX5
Location 9p13
Dna / Rna The PAX5 coding region extends over a genomic interval of approximately 200kb and comprises 10 exons. Two alternative transcripts have been identified, originating from alternative promotor usage, containing exon 1A or 1B. Full length mRNA is 3650bp.
Protein PAX5 belongs to the paired box family of transcription factors, involved in a multitude of developmental processes. PAX5 was originally identified as a B-cell specific transcription factor (B-cell-specific activator protein, BSAP. Recently, it has been shown that PAX5 expression is not only continuously required for B cell lineage commitment during early B cell development but also for B lineage maintenance. Contains a paired box (DNA binding) domain, a truncated homeo domain homology region, and a transactivation domain.
Gene Name ETV6
Location 12p13
Dna / Rna alternative transcripts
Protein contains a HLH domain and a ETS-DNA binding domain; ETS-related transcription factor, transcriptional repressor that binds to DNA sequence 5'- CCGGAAGT-3', can form homodimers or heterodimers with TEL2 or FLI1

Result of the chromosomal anomaly

Hybrid gene
Description fusion of PAX5 to ETV6; constant breakpoints in PAX5 intron 4 and ETV6 intron 2, in the three cases described so far.
Transcript 5'PAX5 - 3'ETV6 transcript, no reciprocal transcript due to deletion
Detection RT-PCR, FISH
  
Fusion Protein
 
Description The PAX5/ETV6 chimeric transcript results in fusion of the paired box domain (PRD) of PAX5 to the helix-loop-hel ix and ETS-binding domains of ETV6. Of note: the putative chimeric protein contains the DNA-binding domains of both fusion partners, namely the PRD and the ETS-domain.
  

To be noted

Bone marrow transplantation should not be performed, as the prognosis of the dic(9;12)/ALL is excellent.

Bibliography

Dicentric (9;12) in acute lymphocytic leukemia and other hematological malignancies: report from a dic(9;12) study group.
Behrendt H, Charrin C, Gibbons B, Harrison CJ, Hawkins JM, Heerema NA, Horschler-Bötel B, Huret JL, Laï JL, Lampert F
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1995 ; 9 (1) : 102-106.
PMID 7845002
 
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 research. 2001 ; 61 (12) : 4666-4670.
PMID 11406533
 
Two additional cases of t dic(9:12) in acute lymphocytic leukemia (ALL): prognosis in ALL with dic(9:12).
Huret JL, Heerema NA, Brizard A, Provisor AJ, Benz-Lemoine E, Guilhot F, Savage JR, Tanzer J
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1990 ; 4 (6) : 423-425.
PMID 2193203
 
The non-random dic(9;12) translocation in acute lymphoblastic leukemia is associated with B-progenitor phenotype and an excellent prognosis.
Mahmoud H, Carroll AJ, Behm F, Raimondi SC, Schuster J, Borowitz M, Land V, Pullen DJ, Vietti TJ, Crist W
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1992 ; 6 (7) : 703-707.
PMID 1625489
 
PAX5/ETV6 fusion defines cytogenetic entity dic(9;12)(p13;p13).
Strehl S, König M, Dworzak MN, Kalwak K, Haas OA
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 ; 17 (6) : 1121-1123.
PMID 12764378
 

Citation

This paper should be referenced as such :
Strehl, S
dic(9;12)(p13;p13)
Atlas Genet Cytogenet Oncol Haematol. 2004;8(2):94-96.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/dic0912ID1065.html
History of this paper:
Huret, JL. dic(9;12)(p11-13;p11-12). Atlas Genet Cytogenet Oncol Haematol. 1997;1(1):15-15.
http://documents.irevues.inist.fr/bitstream/handle/2042/32027/08-1997-dic0912ID1065.pdf
Huret, JL. dic(9;12)(p13;p13). Atlas Genet Cytogenet Oncol Haematol. 2003;7(3):178-180.
http://documents.irevues.inist.fr/bitstream/handle/2042/37988/06-2003-dic0912.pdf


Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

Genes ETV6 PAX5

Translocations implicated (Data extracted from papers in the Atlas)

 dic(9;12)(p13;p13) PAX5/ETV6

External links

PAX5 (9p13.2) ETV6 (12p13.2)

PAX5 (9p13.2) ETV6 (12p13.2)

Mitelman databasedic(9;12)(p13;p13) [Case List]    dic(9;12)(p13;p13) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databasePAX5/ETV6 [MCList]  PAX5 (9p13.2) ETV6 (12p13.2)
TICdbPAX5/ETV6  PAX5 (9p13.2) ETV6 (12p13.2)
 
Disease databasedic(9;12)(p13;p13) PAX5/ETV6
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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