t(2;8)(q12;p11) RANBP2/FGFR1

2014-11-01   Carine Gervais 

1.Laboratoire de Cytogenetique Hematologique, CHU Strasbourg, France

Clinics and Pathology

Disease

Myeloid and lymphoid neoplasms with FGFR1 abnormalities (previously: 8p11 myeloproliferative syndrome)

Note

Different disease phenotypes according to the FGFR1 partner gene.

Phenotype stem cell origin

Pluripotent haematopoietic stem cell.

Epidemiology

Only one case to date, a 63 years old female with myeloproliferative/myelodysplastic neoplasm (Gervais et al., 2013).

Clinics

Splenomegaly, dyspnea, impaired general condition at diagnosis. Rapid disease progression despite chemotherapy.
Atlas Image
Bone marrow (MGG): hypercellularity with granular hyperplasia, dysgranulopoiesis and few eosinophils.

Evolution

Disease progressed rapidly and the patient died 6 months after the diagnosis.

Prognosis

Undetermined (myeloid and lymphoid neoplasms with FGFR1 abnormalities prognosis is currently poor).

Cytogenetics

Atlas Image
R and G-banding showing t(2;8)(q12;p11).

Cytogenetics morphological

t(2;8)(q12;p11) without additional abnormality.
Atlas Image
Cohybridization of FGFR1 BAC RP11-350N15 (8p11, green) and RANBP2 RP11-84C2 (2q12, red) showing a dual fusion signal.

Genes Involved and Proteins

Gene name
FGFR1 (Fibroblast Growth Factor Receptor 1)
Location
8p11.23
Note
Receptor tyrosine kinase.
Dna rna description
18 exons.
Protein description
Extracellular ligand-binding domain (with the N-terminus). Unique transmembrane domain. Catalytic (tyrosine kinase) cytosolic domain.
Gene name
RANBP2 (RAN binding protein 2)
Location
2q12.3
Note
Implicated in various cancers, inflammatory myofibroblastic tumors (with ALK 2p23), JMML and AML with RANBP2-ALK fusion (Rottgers et al., 2010; Maesako et al., 2014; Lim et al., 2014).
Dna rna description
31 exons.
Protein description
Component of the nuclear pore complex, localised at its cytoplasmic side.

Result of the Chromosomal Anomaly

Atlas Image
Schematic representation of RANBP2-FGFR1 fusion transcript.

Description

5 RANBP2 - 3 FGFR1; fusion of RANPB2 exon 20 to FGFR1 exon 9.

Transcript

Detection of both RANBP2-FGFR1 transcript and FGFR1-RANBP2 reciprocal transcript.
Atlas Image
Schematic representation of RANBP2, FGFR1 and RANBP2-FGFR1 predicted fusion protein.

Description

RANBP2 N-terminal (leucine-rich region) - FGFR1 C-terminal (TK domain).

Oncogenesis

Constitutive activation of FGFR1 kinase activity.

Bibliography

Pubmed IDLast YearTitleAuthors
1560934220058p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes.Belloni E et al
117391862001The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins.Demiroglu A et al
117469712001Fusion of the BCR and the fibroblast growth factor receptor-1 (FGFR1) genes as a result of t(8;22)(p11;q11) in a myeloproliferative disorder: the first fusion gene involving BCR but not ABL.Fioretos T et al
230417762013A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm.Gervais C et al
150348732004Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.Grand EK et al
106888392000FGFR1 is fused to the centrosome-associated protein CEP110 in the 8p12 stem cell myeloproliferative disorder with t(8;9)(p12;q33).Guasch G et al
123935972003Endogenous retroviral sequence is fused to FGFR1 kinase in the 8p12 stem-cell myeloproliferative disorder with t(8;19)(p12;q13.3).Guasch G et al
182052092008The t(1;9)(p34;q34) and t(8;12)(p11;q15) fuse pre-mRNA processing proteins SFPQ (PSF) and CPSF6 to ABL and FGFR1.Hidalgo-Curtis C et al
226191102012Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome.Li F et al
240348962013Inflammatory myofibroblastic tumor with RANBP2 and ALK gene rearrangement: a report of two cases and literature review.Li J et al
246132772014RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia.Lim JH et al
126610112003Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor.Ma Z et al
243075152014inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia that developed in an elderly woman.Maesako Y et al
111221152000The 8p12 myeloproliferative disorder. t(8;19)(p12;q13.3): a novel translocation involving the FGFR1 gene.Mugneret F et al
99491821999The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1.Popovici C et al
204281972010ALK fusion genes in children with atypical myeloproliferative leukemia.Röttgers S et al
193699592009LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome.Soler G et al
158006732005The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1.Walz C et al
213303212011The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11).Wasag B et al
94259081998FGFR1 is fused with a novel zinc-finger gene, ZNF198, in the t(8;13) leukaemia/lymphoma syndrome.Xiao S et al

Citation

Carine Gervais

t(2;8)(q12;p11) RANBP2/FGFR1

Atlas Genet Cytogenet Oncol Haematol. 2014-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1661/t(2;8)(q12;p11)

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