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t(7;14)(p15;q11) TRD/HOXA10

Written2006-06Julie Bergeron, Elizabeth Macintyre , Vahid Asnafi
Laboratoire d'Hématologie, INSERM EMI0210, Hôpital Necker-Enfants Malades, Université Paris-Descartes, AP-HP, Paris, France

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
Atlas_Id 1435

Clinics and Pathology

Disease T- Acute lymphoblastic leukemia (T-ALL)
Phenotype / cell stem origin T lineage TCR gamma delta +, CD4/8 double positive (DP), CD1a- immunophenotype
Epidemiology 1 case reported
Clinics FABL1 or L2. The index case had hepatosplenomegaly without mediastinal involvement.

Cytogenetics

Cytogenetics Molecular Balanced t(7;14)
  • Der(7):Intronic region of HOXA locus on 7p15 between HOXA6 and HOXA7 genes fused with Jd1 segment of TCRD on 14q11.
  • Der(14): DREC segment on chromosome 14q11 rearranged with Dd2 and Dd3 segments and fused to the telomeric part of HOXA locus on 7p15
    •  
      Fig1: FISH hybridization result using a TCRA/D distal (Green) and HOXA proximal (orange) FISH probes showing a fusion signal in 6 of 8 mitosis.
    Additional anomalies This case also expressed (by RQ-PCR) a CALM-AF10 fusion transcript (t(10;11)(p13;q14-21)).
    Variants variant translocation cases are reported: 9 cases of T-ALLs having the HOXA locus translocated to TCRB in a t(7;7). The breakpoints on 7p15 in those HOXA-TCRB cases are more centromeric, close to HOXA9

    Genes involved and Proteins

    Gene Name HOXA@
    Location 7p15
    Note HOXA6 and HOXA7 lie at 6,9kb from each other on 7p15
    Protein various HOXA genes act as transcription factors playing important roles in the differentiation and commitment processes of embryonic and hematopoietic cells.
    Gene Name TRD
    Location 14q11
    Note Breakpoint on der(7) lie 5' from Jd1. Breakpoint on der(14)lies 12 nucleotides 5' of the 3' end of the DREC segment.
    Protein Protein encoded by the TCRD locus are the T-cell receptor chains.

    Result of the chromosomal anomaly

    Hybrid gene
      Fig2: Sequence of events leading to the final translocation. Exons are represented by boxes. Triangles represent RSS and show their orientation. E=enhancer.
     
      
    Fusion Protein
     
      Fig3: The nucleotide sequence of both derivatives implicated in the t(7 ;14) translocation. Underscored are RSS or RSS-like sequence in the vincinity of the breakpoints. In lower case letters: non templated nucleotides at the junction.
    Description No fusion protein. Overexpression of HOXA genes as a result of the translocation with TCRD was expected, as it was demonstrated to be the case in HOXA-TCRB T-ALLs. However this case had a CALM-AF10 fusion in the same leukemic clone. CALM-AF10 is already known to be associated with HOXA cluster global overexpression. The HOXA pattern of expression in this case was similar to other CALM-AF10 T-ALL.
    Oncogenesis Probable, as several HOX/HOXA genes have been implicated in leukemic processes.
      

    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.
    Case Report T-cell acute lymphoblastic leukemia with t(7;14)(p15;q11.2)/HOXA-TCRA/D and biallelic deletion of CDKN2A. Case report and literature review

    Bibliography

    MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia.
    Armstrong SA, Staunton JE, Silverman LB, Pieters R, den Boer ML, Minden MD, Sallan SE, Lander ES, Golub TR, Korsmeyer SJ
    Nature genetics. 2002 ; 30 (1) : 41-47.
    PMID 11731795
     
    Age-related phenotypic and oncogenic differences in T-cell acute lymphoblastic leukemias may reflect thymic atrophy.
    Asnafi V, Beldjord K, Libura M, Villarese P, Millien C, Ballerini P, Kuhlein E, Lafage-Pochitaloff M, Delabesse E, Bernard O, Macintyre E
    Blood. 2004 ; 104 (13) : 4173-4180.
    PMID 15054041
     
    CALM-AF10 is a common fusion transcript in T-ALL and is specific to the TCRgammadelta lineage.
    Asnafi V, Radford-Weiss I, Dastugue N, Bayle C, Leboeuf D, Charrin C, Garand R, Lafage-Pochitaloff M, Delabesse E, Buzyn A, Troussard X, Macintyre E
    Blood. 2003 ; 102 (3) : 1000-1006.
    PMID 12676784
     
    HOXA cluster deregulation in T-ALL associated with both a TCRD-HOXA and a CALM-AF10 chromosomal translocation.
    Bergeron J, Clappier E, Cauwelier B, Dastugue N, Millien C, Delabesse E, Beldjord K, Speleman F, Soulier J, Macintyre E, Asnafi V
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2006 ; 20 (6) : 1184-1187.
    PMID 16572206
     
    CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes.
    Dik WA, Brahim W, Braun C, Asnafi V, Dastugue N, Bernard OA, van Dongen JJ, Langerak AW, Macintyre EA, Delabesse E
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (11) : 1948-1957.
    PMID 16107895
     
    V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites.
    Marculescu R, Le T, Simon P, Jaeger U, Nadel B
    The Journal of experimental medicine. 2002 ; 195 (1) : 85-98.
    PMID 11781368
     
    MLL targets SET domain methyltransferase activity to Hox gene promoters.
    Milne TA, Briggs SD, Brock HW, Martin ME, Gibbs D, Allis CD, Hess JL
    Molecular cell. 2002 ; 10 (5) : 1107-1117.
    PMID 12453418
     
    HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL).
    Soulier J, Clappier E, Cayuela JM, Regnault A, García-Peydró M, Dombret H, Baruchel A, Toribio ML, Sigaux F
    Blood. 2005 ; 106 (1) : 274-286.
    PMID 15774621
     
    A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias.
    Speleman F, Cauwelier B, Dastugue N, Cools J, Verhasselt B, Poppe B, Van Roy N, Vandesompele J, Graux C, Uyttebroeck A, Boogaerts M, De Moerloose B, Benoit Y, Selleslag D, Billiet J, Robert A, Huguet F, Vandenberghe P, De Paepe A, Marynen P, Hagemeijer A
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (3) : 358-366.
    PMID 15674412
     

    Citation

    This paper should be referenced as such :
    Bergeron, J ; Macintyre, E ; Asnafi, V
    t(7;14)(p15;q11)
    Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):279-281.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Anomalies/t0714p15q11ID1435.html

    Translocations implicated (Data extracted from papers in the Atlas)

     t(7;14)(p15;q11) TRD/HOXA10

    External links

    Mitelman databaset(7;14)(p15;q11) [Case List]    t(7;14)(p15;q11) [Association List] Mitelman database (CGAP - NCBI)
    arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
     
     
    Disease databaset(7;14)(p15;q11) TRD/HOXA10
    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 11:23:23 CEST 2017

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