t(8;13)(p11;q12) ZMYM2/FGFR1
2000-12-01 Marie-Josçphe Pébusque , Marie-Josçphe Pébusque Affiliation1.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
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
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 27245147 | 2016 | FGFR inhibitors: Effects on cancer cells, tumor microenvironment and whole-body homeostasis (Review). | 137 |
| 35013300 | 2022 | A proximity biotinylation-based approach to identify protein-E3 ligase interactions induced by PROTACs and molecular glues. | 66 |
| 21527531 | 2011 | Constitutive Notch pathway activation in murine ZMYM2-FGFR1-induced T-cell lymphomas associated with atypical myeloproliferative disease. | 54 |
| 34027417 | 2021 | Avadomide induces degradation of ZMYM2 fusion oncoproteins in hematologic malignancies. | 49 |
| 27415155 | 2016 | Diagnostic application of next-generation sequencing in ZMYM2-FGFR1 8p11 myeloproliferative syndrome: A case report. | 22 |
| 22875613 | 2013 | Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome. | 19 |
| 22875628 | 2013 | Ruxolitinib as potential targeted therapy for patients with JAK2 rearrangements. | 18 |
| 27005999 | 2016 | Development of ZMYM2-FGFR1 driven AML in human CD34+ cells in immunocompromised mice. | 16 |
| 37275466 | 2023 | Myeloid/lymphoid neoplasm with ZMYM2::FGFR1 rearrangement: A complex trilineage phenotypic and clonal evolution with associated genomic alterations. | 10 |
| 23751892 | 2013 | A ZMYM2-FGFR1 8p11 myeloproliferative neoplasm with a novel nonsense RUNX1 mutation and tumor lysis upon imatinib treatment. | 0 |
| 37435901 | 2023 | Concomitant myeloproliferative neoplasm with eosinophilia, B and T cell lymphoblastic lymphoma/leukemia and mast cell proliferation driven by ZMYM2::FGFR1 rearrangement. | 0 |
| 30160587 | 2019 | ZMYM2-FGFR1 fusion as secondary change in acute myeloid leukemia. | 0 |
| 28551329 | 2017 | Myeloproliferative neoplasms with t(8;22)(p11.2;q11.2)/BCR-FGFR1: a meta-analysis of 20 cases shows cytogenetic progression with B-lymphoid blast phase. | 0 |
| 20554971 | 2010 | Modeling the human 8p11-myeloproliferative syndrome in immunodeficient mice. | 0 |
| 22236811 | 2012 | Submicroscopic deletion of FGFR1 gene is recurrently detected in myeloid and lymphoid neoplasms associated with ZMYM2-FGFR1 rearrangements: a case study. | 0 |
| 29107667 | 2018 | FGFR1 translocation with concurrent myeloproliferative neoplasm, systemic mastocytosis, and lymphoblastic lymphoma: a case report. | 0 |
| 27569099 | 2016 | 8p11 myeloproliferative syndrome: diagnostic challenges and pitfalls. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9376594 | 1997 | Abnormalities of chromosome band 8p11 in leukemia: two clinical syndromes can be distinguished on the basis of MOZ involvement. | Aguiar RC et al |
| 9889006 | 1999 | The genomic structure of ZNF198 and location of breakpoints in the t(8;13) myeloproliferative syndrome. | Kulkarni S et al |
| 10480903 | 1999 | Characterization of FIM-FGFR1, the fusion product of the myeloproliferative disorder-associated t(8;13) translocation. | Ollendorff V et al |
| 9576949 | 1998 | Fibroblast growth factor receptor 1 is fused to FIM in stem-cell myeloproliferative disorder with t(8;13). | Popovici C et al |
| 9716603 | 1998 | Consistent fusion of ZNF198 to the fibroblast growth factor receptor-1 in the t(8;13)(p11;q12) myeloproliferative syndrome. | Reiter A et al |
| 10935490 | 1999 | ZNF198-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 |
| 9499416 | 1998 | 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 et al |
| 10887137 | 2000 | ZNF198-FGFR1 transforming activity depends on a novel proline-rich ZNF198 oligomerization domain. | Xiao S et al |
| 9425908 | 1998 | FGFR1 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
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)-zmym2-fgfr1
Historical Card
1998-03-01 t(8;13)(p11;q12) ZMYM2/FGFR1 by Dominique Leroux,Alain Bernheim,Jean-Loup Huret Affiliation
Lymphoma Research Group - Groupe de Recherche sur les Lymphomes, Institut Albert Bonniot, La Tronche 38706, France (DL)
