t(8;12)(p12;p11) FGFR1OP2/FGFR1
ins(12;8)(p11;p12p22) FGFR1OP2/FGFR1

2007-12-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Non Hodgkin lymphoma (NHL) associated with myeloproliferative disease (MPD), typical of the 8p11 myeloproliferative syndrome (EMS)

Epidemiology

Only one case to date, a 75 year old male patient

Clinics

The patient presented with a T-cell lymphoblastic Lymphoma. Complete remission was obtained on treatment, but a relapse occurred and the patient developped an acute myeloid leukaemia (AML) and died 3 months later.

Genes Involved and Proteins

Gene name
FGFR1 (Fibroblast Growth Factor Receptor 1)
Location
8p11.23
Protein description
FGF receptor with tyrosine kinase activity; binding of ligand induces receptor dimerization, autophosphorylation and signal transduction
Gene name
FGFR1OP2 (FGFR1 oncogene partner 2)
Location
12p11.23
Protein description
Poorly known; expressed in various tissues; no significant homology to any known protein; comprises coiled-ciol domains

Result of the Chromosomal Anomaly

Description

5 FGFR1OP2 - 3 FGFR1; in frame fusion of exon 4 of FGFR1OP2 to exon 9 of FGFR1 (nucleotide 1817 of FGFR1OP2 intron 4 joined to nucleotide 1132 of FGFR1 intron 8). Reciprocal transcripts were not detected. The direction of transcription of FGFR1OP2 is telomere to centromere, while FGFR1s transcription is centromere to telomere, implying an inversionThe first 2 coiled-coil domains of FGFR1OP2 is fused to the COOH terminal part of FGFR1, including part of its juxta membrane domain, and its tyrosine kinase domain: 132 amino acids from FGFR1OP2 and 394 from FGFR1. The FGFR1OP2-FGFR1 fusion protein may exhibit constitutive kinase activity, inducing dimerization, constitutive signal transduction, and be responsible for transforming activity.

Highly cited references

Pubmed IDYearTitleCitations
322472632020GZD824 as a FLT3, FGFR1 and PDGFRα Inhibitor Against Leukemia In Vitro and In Vivo.5
295624502018[Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells].1
265899152016FGFR1OP2-FGFR1 induced myeloid leukemia and T-cell lymphoma in a mouse model.10
263914362016Functional characterization, localization, and inhibitor sensitivity of the TPR-FGFR1 fusion in 8p11 myeloproliferative syndrome.4
228756132013Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome.23
217455652011The driver of malignancy in KG-1a leukemic cells, FGFR1OP2-FGFR1, encodes an HSP90 addicted oncoprotein.9
215275312011Constitutive Notch pathway activation in murine ZMYM2-FGFR1-induced T-cell lymphomas associated with atypical myeloproliferative disease.25
211988592011The 8p11 myeloproliferative syndrome owing to rare FGFR1OP2-FGFR1 fusion.3
205875022010Targeted next-generation sequencing of DNA regions proximal to a conserved GXGXXG signaling motif enables systematic discovery of tyrosine kinase fusions in cancer.21
176986332007Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome.39
17389761200714-3-3 Integrates prosurvival signals mediated by the AKT and MAPK pathways in ZNF198-FGFR1-transformed hematopoietic cells.25
322472632020GZD824 as a FLT3, FGFR1 and PDGFRα Inhibitor Against Leukemia In Vitro and In Vivo.5
295624502018[Inhibitory Eefects of the novel tyrosine kinase inhibitor BGJ398 against human leukemic cell line KG-1 cells].1
265899152016FGFR1OP2-FGFR1 induced myeloid leukemia and T-cell lymphoma in a mouse model.10
263914362016Functional characterization, localization, and inhibitor sensitivity of the TPR-FGFR1 fusion in 8p11 myeloproliferative syndrome.4
228756132013Ponatinib as targeted therapy for FGFR1 fusions associated with the 8p11 myeloproliferative syndrome.23
217455652011The driver of malignancy in KG-1a leukemic cells, FGFR1OP2-FGFR1, encodes an HSP90 addicted oncoprotein.9
215275312011Constitutive Notch pathway activation in murine ZMYM2-FGFR1-induced T-cell lymphomas associated with atypical myeloproliferative disease.25
211988592011The 8p11 myeloproliferative syndrome owing to rare FGFR1OP2-FGFR1 fusion.3
205875022010Targeted next-generation sequencing of DNA regions proximal to a conserved GXGXXG signaling motif enables systematic discovery of tyrosine kinase fusions in cancer.21
176986332007Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome.39
17389761200714-3-3 Integrates prosurvival signals mediated by the AKT and MAPK pathways in ZNF198-FGFR1-transformed hematopoietic cells.25

Bibliography

Pubmed IDLast YearTitleAuthors
150348732004Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.Grand EK et al

Summary

Fusion gene

FGFR1OP2/FGFR1 FGFR1OP2 (12p11.23) FGFR1 (8p11.23) M|FGFR1OP2/FGFR1 FGFR1OP2 (12p11.23) FGFR1 (8p11.23) M ins(12;8)(p11;p11p22)|FGFR1OP2/FGFR1 FGFR1OP2 (12p11.23) FGFR1 (8p11.23) TIC

Citation

Jean-Loup Huret

t(8;12)(p12;p11) FGFR1OP2/FGFR1
ins(12;8)(p11;p12p22) FGFR1OP2/FGFR1

Atlas Genet Cytogenet Oncol Haematol. 2007-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1330/t(8;12)(p12;p11)-fgfr1op2-fgfr1-br-ins(12;8)(p11;p12p22)-fgfr1op2-fgfr1

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