Atlas of Genetics and Cytogenetics in Oncology and Haematology
dic(9;12)(p13;p13)
| Identity |
 | |
| dic(9;12)(p13;p13) diagram and breakpoints and C-banding (above) - Editor; G- banding (left) - Courtesy Jean-Luc Lai; R- banding with chr 12 up side down (right)- Editor | |
| 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 |
| 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 |
| 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. |
| External links |
| Other database | dic(9;12)(p13;p13) | Mitelman database (CGAP - NCBI) |
| To be noted |
| Bone marrow transplantation should not be performed, as the prognosis of the dic(9;12)/ALL is excellent. Cases with dic(9;12) involvement are collected and analyzed for the presence of the PAX5/ETV6 fusion. If you are interested in participating in this study, please contact: sabine.strehl@ccri.at |
| Bibliography |
| 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 |
| 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-Btel B, Huret JL, La 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 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 |
| 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 |
| PAX5/ETV6 fusion defines cytogenetic entity dic(9;12)(p13;p13). |
| Strehl S, Knig 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 |
| Contributor(s) |
| Written | 08-1997 | Jean-Loup Huret |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France | ||
| Updated | 06-2003 | Jean-Loup Huret |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France | ||
| Updated | 01-2004 | Sabine Strehl |
| CCRI, Children's Cancer Research Institute St. Anna Kinderkrebsforschung Kinderspitalgasse 6 A-1090, Vienna, Austria |
| Citation |
| This paper should be referenced as such : |
| Huret JL . dic(9;12)(p13;p13). Atlas Genet Cytogenet Oncol Haematol. August 1997 . URL : http://AtlasGeneticsOncology.org/Genes/dic0912.html |
| Huret JL . dic(9;12)(p13;p13). Atlas Genet Cytogenet Oncol Haematol. June 2003 . URL : http://AtlasGeneticsOncology.org/Genes/dic0912.html |
| Strehl S . dic(9;12)(p13;p13). Atlas Genet Cytogenet Oncol Haematol. January 2004 . URL : http://AtlasGeneticsOncology.org/Genes/dic0912.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Jul 14 16:32:20 2008 |
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