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t(8;9)(p12;q33) CNTRL/FGFR1

Written2004-01Jacques Boyer
Laboratoire d' hématologie, CH du MANS, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9967/3 Myeloid and lymphoid neoplasms with FGFR1 rearrangement
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
Atlas_Id 1129
Note 8p12 myeloproliferative syndrome (EMS) / stem cell leukemia-lymphoma syndrome (SCLL) belongs to the tyrosine kinase fusion genes chronic myeloproliferative diseases .
It is associated with recurent translocations :
  • t(6;8)(q27;p12),
  • t(8;9)(p12;q33),
  • t(8;11)(p12;p15),
  • t(8;12)(p12;q15),
  • t(8;13)(p12;q12),
  • t(8;17)(p12;q25),
  • t(8;19)(p12;q13),
  • t(8;22)(p12;q11)
  •  
      t(8;9)(p12;q33) G- banding - Courtesy Melanie Zenger and Claudia Haferlach.

    Clinics and Pathology

    Disease Myeloproliferative disorder that is frequently associated with T-cell, or less commonly B-cell non Hodgkin lymphoma.
    Phenotype / cell stem origin May involve a stem cell.
    Epidemiology 9 cases are described ; sexe ratio : 6M/3F.
    Clinics Agressive disease ; myeloid hyperplasia progressing to myelodysplasia and T or B-cell lymphoma, splenomegaly, lymph node.
    High WBC with myelemia with frequently eosinophilia and sometimes monocytosis (near CMLL).
    Evolution The disease transforms to AML or occasionally ALL in a median of 6 months.
    Prognosis Median survival : 12 months.

    Cytogenetics

    Cytogenetics Morphological This translocation is a variant of the t(8 ;13)(p12 ;q12).
    Additional anomalies +der(9), +21

    Genes involved and Proteins

    Gene Name FGFR1
    Location 8p12
    Gene Name CNTRL
    Location 9q33
    Dna / Rna DNA : 26kb - 19 exons
    RNA : Three mains transcripts of approximatly 7.5, 4.5 and 1.5 kb. CEP transcripts are barely expressed in thymus and peripheral blood cells.
    Protein CEP110 gene codes for a 994-amino acid coiled-coil protein with 4 consensus leucine zippers (centrosome associated P110 protein).

    Result of the chromosomal anomaly

    Hybrid gene
    Description The t(8;9) breakpoint in the FGFR1 gene is localized in exon 8, 12 bp upstream of the exon 8/intron 8 junction. It is distinct from the breakpoints in the t(6;8) and t(8;13) but it preserves the same FGFR1 sequence in the chimeric protein.
    The breakpoint in the CEP110 is localized in exon 15.
    The translocation leads to the formation of the two reciprocal transcripts.
      
    Fusion Protein
    Description
  • The CEP110-FGFR1 fusion protein encodes an aberrant tyrosine kinase of 150-kd wich retains most of CEP110 with the leucine zipper motif and the catalytic domain of FGFR1.
  • The CEP110-FGFR1 protein has a constitutive kinase activity and is located within the cell cytoplasm contrasting with the centrosome and membrane localizations of the wildtype respective proteins.
  • The FGFR1-CEP110 protein contains the FGFR1 N-terminal region with its ligand-binding and transmembrane domains and the CEP110 C-terminal region.
  • Oncogenesis Activated aberrant tyrosine kinase are likely to promote leukemogenesis through contitutive activation of the FGFR1 kinase. This activation may be mediated by dimerisation of the portion of the fusion protein wich contains the leucine zippers.
    This activation may interacts with the cell proliferation and the apoptose, additional anomalies may also play an important role in the evolution of the disease.
      

    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 Translocation t(8;9)(p12;q33) detected in cALL: A case report

    Bibliography

    Tyrosine kinase fusion genes in chronic myeloproliferative diseases.
    Cross NC, Reiter A
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 ; 16 (7) : 1207-1212.
    PMID 12094244
     
    FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).
    Guasch G, Mack GJ, Popovici C, Dastugue N, Birnbaum D, Rattner JB, Pébusque MJ
    Blood. 2000 ; 95 (5) : 1788-1796.
    PMID 10688839
     
    The 8p11 myeloproliferative syndrome: a distinct clinical entity caused by constitutive activation of FGFR1.
    Macdonald D, Reiter A, Cross NC
    Acta haematologica. 2002 ; 107 (2) : 101-107.
    PMID 11919391
     
    R?éarrangements chromosomiques et syndromes my?éloprolif?é mixtes.
    Popovici C
    Thè Aix Marseille II,. 1998.
     
    Identification of four new translocations involving FGFR1 in myeloid disorders.
    Sohal J, Chase A, Mould S, Corcoran M, Oscier D, Iqbal S, Parker S, Welborn J, Harris RI, Martinelli G, Montefusco V, Sinclair P, Wilkins BS, van den Berg H, Vanstraelen D, Goldman JM, Cross NC
    Genes, chromosomes & cancer. 2001 ; 32 (2) : 155-163.
    PMID 11550283
     

    Citation

    This paper should be referenced as such :
    Boyer, J
    t(8;9)(p12;q33)
    Atlas Genet Cytogenet Oncol Haematol. 2004;8(2):92-93.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://AtlasGeneticsOncology.org/Anomalies/t0809p12q33ID1129.html


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

    Genes FGFR1

    Translocations implicated (Data extracted from papers in the Atlas)

     t(8;9)(p12;q33) CNTRL/FGFR1

    External links

    CNTRL (9q33.2) FGFR1 (8p11.23)

    CNTRL (9q33.2) FGFR1 (8p11.23)

    CNTRL (9q33.2) FGFR1 (8p11.23)

    Mitelman databaset(8;9)(p12;q33) [Case List]    t(8;9)(p12;q33) [Association List] Mitelman database (CGAP - NCBI)
    arrayMapTopo ( C42) Morph ( 9967/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMapTopo ( C42) Morph ( 9975/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
     
    Mitelman databaseCNTRL/FGFR1 [MCList]  CNTRL (9q33.2) FGFR1 (8p11.23)
    Mitelman databaseCNTRL/FGFR1 [MCList]  CNTRL (9q33.2) FGFR1 (8p11.23)
    TICdbCNTRL/FGFR1  CNTRL (9q33.2) FGFR1 (8p11.23)
     
    Disease databaset(8;9)(p12;q33) CNTRL/FGFR1
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed


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