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t(8;13)(p11;q12) ZMYM2/FGFR1

Written1998-03Jean-Loup Huret, Dominique Leroux, Alain Bernheim
Lymphoma Research Group - Groupe de Recherche sur les Lymphomes, Institut Albert Bonniot, La Tronche 38706, France (DL)
Updated2000-12Marie-Josçphe Pébusque, Nicholas CP Cross
INSERM U119, IFR 57, 27 Blvd Lei Roure, 13009 Marseille, 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 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1094
 
  t(8;13)(p12;q12) G- banding - Top: Courtesy Melanie Zenger and Claudia Haferlach; Middle and bottom: Courtesy Charles Bangs and Patty Jones.

Clinics and Pathology

Disease a 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 involving both myeloid, T lineage, and B-cell lineage
Epidemiology 14 cases are described; median age 43 yrs (range 18-68); sex ratio: 6M/8F
Clinics aggressive disease; complex picture of myeloid hyperplasia progressing to myelodysplasia and Tor -B- cell lymphoma; enlarged lymph node; blood data: high WBC (median 40 X 109/l); myelemia; monocytosis and eosinophilia
Evolution the disease transforms to AML, or occasionally ALL, in a median of 6 months
Prognosis median survival: 12 months

Cytogenetics

Cytogenetics Morphological the same t(8;13) is found both in the bone marrow and in the lymph node, ruling out the hypothesis of a leukemoid reaction caused by a lymphoma; the multilineage involvement suggests the malignant transformation of a primitive hematopoietic stem cell.
Additional anomalies usually occurs as a single anomaly; duplication of the der(13) was found during disease progression, suggesting that the crucial event might lie on this derivative chromosome; +8, +21 are also recurrently found

Genes involved and Proteins

Gene Name FGFR1
Location 8p12
Gene Name ZMYM2
Location 13q12
Protein zinc finger protein (ten repeats in the N-terminal region with the consensus sequence C-X2-C-X18-24-(F/Y)-C-X3-C that corresponds to a novel type of zing finger motifs), a hydrophobic repeat (proline-rich), and potentially two putative nuclear localisation signals

Result of the chromosomal anomaly

Hybrid gene
 
Description breakpoint in FGFR1 intron 8
  
Fusion Protein
Description Aberrant tyrosine kinase composed of the N-term two-thirds of FIM (retaining the 10 putative zinc finger motifs), and the FGFR1 intracellular region minus the major part of the juxtamembrane domain (and deleting the N-term immunoglobulin-like and central transmembrane domains of FGFR1)
Expression Localisation cytoplasmic
Oncogenesis through constitutive activation of FGFR1 signal transduction pathways, possibly via dimerization capability mediated by the FIM N-term sequences of the fusion protein
  

To be noted

Case Report t(8;13)(p12;q12) in an atypical chronic myeloid leukaemia case

Bibliography

Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement.
Aguiar RC, Chase A, Coulthard S, Macdonald DH, Carapeti M, Reiter A, Sohal J, Lennard A, Goldman JM, Cross NC
Blood. 1997 ; 90 (8) : 3130-3135.
PMID 9376594
 
The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome.
Kulkarni S, Reiter A, Smedley D, Goldman JM, Cross NC
Genomics. 1999 ; 55 (1) : 118-121.
PMID 9889006
 
Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation.
Ollendorff V, Guasch G, Isnardon D, Galindo R, Birnbaum D, Pébusque MJ
The Journal of biological chemistry. 1999 ; 274 (38) : 26922-26930.
PMID 10480903
 
Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13).
Popovici C, Adélaïde J, Ollendorff V, Chaffanet M, Guasch G, Jacrot M, Leroux D, Birnbaum D, Pébusque MJ
Proceedings of the National Academy of Sciences of the United States of America. 1998 ; 95 (10) : 5712-5717.
PMID 9576949
 
Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome.
Reiter A, Sohal J, Kulkarni S, Chase A, Macdonald DH, Aguiar RC, Gonçalves C, Hernandez JM, Jennings BA, Goldman JM, Cross NC
Blood. 1998 ; 92 (5) : 1735-1742.
PMID 9716603
 
ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.
Smedley D, Demiroglu A, Abdul-Rauf M, Heath C, Cooper C, Shipley J, Cross NC
Neoplasia (New York, N.Y.). 1999 ; 1 (4) : 349-355.
PMID 10935490
 
The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP.
Smedley D, Hamoudi R, Clark J, Warren W, Abdul-Rauf M, Somers G, Venter D, Fagan K, Cooper C, Shipley J
Human molecular genetics. 1998 ; 7 (4) : 637-642.
PMID 9499416
 
ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain.
Xiao S, McCarthy JG, Aster JC, Fletcher JA
Blood. 2000 ; 96 (2) : 699-704.
PMID 10887137
 
FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome.
Xiao S, Nalabolu SR, Aster JC, Ma J, Abruzzo L, Jaffe ES, Stone R, Weissman SM, Hudson TJ, Fletcher JA
Nature genetics. 1998 ; 18 (1) : 84-87.
PMID 9425908
 

Citation

This paper should be referenced as such :
Pébusque, MJ ; Cross, NCP
t(8;13)(p12;q12)
Atlas Genet Cytogenet Oncol Haematol. 2001;5(1):39-41.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t813ID1094.html
History of this paper:
Huret, JL ; Leroux, D ; Bernheim, A. t(8;13)(p12;q12). Atlas Genet Cytogenet Oncol Haematol. 1998;2(3):95-96.
http://documents.irevues.inist.fr/bitstream/handle/2042/37440/03-1998-t813ID1094.pdf


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

Genes FGFR1 ZMYM2

Translocations implicated (Data extracted from papers in the Atlas)

 t(8;13)(p11;q12) ZMYM2/FGFR1

External links

ZMYM2 (13q12.11) FGFR1 (8p11.23)

ZMYM2 (13q12.11) FGFR1 (8p11.23)

Mitelman databaset(8;13)(p11;q12) [Case List]    t(8;13)(p11;q12) [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 ( 9989/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseZMYM2/FGFR1 [MCList]  ZMYM2 (13q12.11) FGFR1 (8p11.23)
TICdbZMYM2/FGFR1  ZMYM2 (13q12.11) FGFR1 (8p11.23)
 
Disease databaset(8;13)(p11;q12) ZMYM2/FGFR1
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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