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

2000-12-01   Marie-Josçphe Pébusque , Marie-Josçphe Pébusque 

1.INSERM U119, IFR 57, 27 Blvd Lei Roure, 13009 Marseille, France
2.Lymphoma Research Group - Groupe de Recherche sur les Lymphomes, Institut Albert Bonniot, La Tronche 38706, France (DL)

Clinics and Pathology

Disease

a myeloproliferative disorder that is frequently associated with T cell, or less commonly, B-cell non Hodgkin lymphoma

Phenotype stem cell 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 (Fibroblast Growth Factor Receptor 1)
Location
8p11.23
Gene name
ZMYM2 (fused in myeloproliferative disorders).
Location
13q12.11
Protein description
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

Atlas Image

Description

breakpoint in FGFR1 intron 8Aberrant 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

Bibliography

Pubmed IDLast YearTitleAuthors
93765941997Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement.Aguiar RC et al
98890061999The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome.Kulkarni S et al
104809031999Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation.Ollendorff V et al
95769491998Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13).Popovici C et al
97166031998Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome.Reiter A et al
109354901999ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in high level tyrosine phosphorylation of STATS 1 and 5.Smedley D et al
94994161998The 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 et al
108871372000ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain.Xiao S et al
94259081998FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome.Xiao S et al

Summary

Fusion gene

ZMYM2/FGFR1 ZMYM2 (13q12.11) FGFR1 (8p11.23) M t(8;13)(p11;q12)|ZMYM2/FGFR1 ZMYM2 (13q12.11) FGFR1 (8p11.23) TIC
Atlas Image
t(8;13)(p12;q12) G- banding - Top: Courtesy Melanie Zenger and Claudia Haferlach; Middle and bottom: Courtesy Charles Bangs and Patty Jones.

Citation

Marie-Josçphe Pébusque ; Marie-Josçphe Pébusque

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

Atlas Genet Cytogenet Oncol Haematol. 2000-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1094/t(8;13)(p11;q12)

Historical Card

1998-03-01 t(8;13)(p11;q12) ZMYM2/FGFR1 by  Dominique Leroux,Alain Bernheim,Jean-Loup Huret 

Lymphoma Research Group - Groupe de Recherche sur les Lymphomes, Institut Albert Bonniot, La Tronche 38706, France (DL)

External Links