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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
Updated2017-09Adriana Zamecnikova
Kuwait Cancer Control Center, Department of Hematology, Laboratory of Cancer Genetics, Kuwait; annaadria@yahoo.com

Abstract Review on t(7;14)(p15;q11) TRD/HOXA10, with data on clinics.

Keywords Chromosome 7; Chromosome 14; TRD ; HOXA10; T-cell lymphoblastic leukaemia

(Note : for Links provided by Atlas : click)

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-cell Acute lymphoblastic leukemia (T-ALL)
Phenotype / cell stem origin T lineage TCR gamma delta +, CD4/8 double positive (DP), CD1a- ; FAB L1 or L2 immunophenotype
Epidemiology 2 patients diagnosed with T-cell acute lymphoblastic leukemia: a 29-years old male (Asnafi et al., 2003) and a 9- years old male (Mahlow et al., 2015). In addition, 3 more cases with t(7;14)(p15;q11) have been described: a 51-years old male with mycosis fungoides/Sezary syndromeand TRA+ rearrangement (Santos et al., 1990), a 31-year old female with T-ALL (Garipidou et al., 1991) and a 46-years old female with refractory anemia with excess of blasts and rearranged HOXA9 (Chen et al., 2005) (Table 1).
Table 1. Reported cases with t(7;14)(p15;q11)
 Sex/AgeDiagnosisKaryotypeGenes involved
4F/46 RAEB 46,XX,t(7;14)(p15;q11),+8HOXA9/?
2F/31 T-ALL 46,XX,t(7;14)(p15;q11),add(18)(q23) ?
3M/29 T-ALL46,XY,t(7;14)(p15;q11),t(10;11)(p14;q21),add(18)(q23)HOXA-TRA/D
CALM-AF10
59/M T-ALL46,XY,del(6)(q14q21),t(7;14)(p15;q11.2),del(9)(p13)/92,idemx2 HOXA-TRA/D
1M/51Mycosis fungoides/ Sezary syndrome41-45,X,-Y,add(5)(q33),+7,t(7;14)(p15;q11),-8,-10,del(10)(p13), del(11)(q21q23),del(12)(p13),add(14)(q11),add(15)(q15),incTRA+, TRG+
)
1. Santos et al., 1990; 2. Garipidou et al., 1991; 3.Asnafi et al., 2003; 4. Chen et al., 2005; 5. Mahlow et al., 2015.Abbreviations: M: male; F: female; T-ALL: T-cell acute lymphoblastic leukemia, RAEB: refractory anemia with excess of blasts.

Cytogenetics

 
  Figure 1. FISH hybridization result using a TCRA/D distal (Green) and HOXA proximal (orange) FISH probes showing a fusion signal - Courtesy Julie Bergeron, Elizabeth Macintyre , Vahid Asnaf.
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
  •  
      Figure 2. (A) Partial karyotypes showing t(7;14)(p15.2;q11.2). (B) Fluorescence in situ hybridization with LSI TCRA/D break apart probe (Vysis, Abbott Moleculars, US) showing TCRA/D rearrangement as a result of t(7;14)(p15.2;q11.2) - Courtesy Adriana Zamecnikova.
    Additional anomalies The case described by Asnafi et al. 2003 also expressed (by RQ-PCR) a CALM-AF10 fusion transcript (t(10;11)(p13;q14-21)). Associated with 6q and 9pdeletion in the other T-ALL case with fusion of HOXA-TCRA/D gene regions (Mahlow et al., 2015).
    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 NameHOXA@
    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 NameTRD (T cell Receptor Delta)
    Location 14q11.2
    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
      Figure 3. Sequence of events leading to the final translocation. Exons are represented by boxes. Triangles represent RSS and show their orientation. E=enhancer- Courtesy Julie Bergeron, Elizabeth Macintyre , Vahid Asnaf..
     
      
    Fusion Protein
     
      Figure 4. 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- Courtesy Julie Bergeron, Elizabeth Macintyre , Vahid Asnaf..
    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
    Nat Genet 2002 Jan;30(1):41-7
    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 Dec 15;104(13):4173-80
    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 Aug 1;102(3):1000-6
    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 2006 Jun;20(6):1184-7
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    Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in Western countries
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    CALM-AF10+ T-ALL expression profiles are characterized by overexpression of HOXA and BMI1 oncogenes
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    The use of fluorodeoxyuridine synchronization for cytogenetic investigation of acute lymphoblastic leukemia
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    Cancer Genet Cytogenet 1991 Mar;52(1):107-11
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    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.
    Mahlow J, Ebrahim S, Mohamed AN.
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    V(D)J-mediated translocations in lymphoid neoplasms: a functional assessment of genomic instability by cryptic sites
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    Mol Cell 2002 Nov;10(5):1107-17
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    Possible correlation between a specific alteration t(7;14) and the rearrangement of TCR observed in a Sézary's syndrome
    Santos M, Benitez J, Rivas C
    Cancer Genet Cytogenet 1990 Jun;46(2):281-3
    PMID 2340497
     
    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 Jul 1;106(1):274-86
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    A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias
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    Citation

    This paper should be referenced as such :
    Zamecnikova A
    t(7;14)(p15;q11) TRD/HOXA10;
    Atlas Genet Cytogenet Oncol Haematol. in press
    On line version : http://AtlasGeneticsOncology.org/Anomalies/t0714p15q11ID1435.html
    History of this paper:
    Bergeron, J ; Macintyre, E ; Asnafi, V. t(7;14)(p15;q11). Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):279-281.
    http://documents.irevues.inist.fr/bitstream/handle/2042/38363/06-2006-t0714p15q11ID1435.pdf


    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 : Mon Nov 20 21:37:29 CET 2017


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