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

2014-11-01 Carine Gervais Affiliation

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.

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

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

Cytogenetics morphological

t(2;8)(q12;p11) without additional abnormality.

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

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.

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.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
15609342	2005	8p11 myeloproliferative syndrome with a novel t(7;8) translocation leading to fusion of the FGFR1 and TIF1 genes.	Belloni E et al
11739186	2001	The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins.	Demiroglu A et al
11746971	2001	Fusion 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
23041776	2013	A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm.	Gervais C et al
15034873	2004	Identification of a novel gene, FGFR1OP2, fused to FGFR1 in 8p11 myeloproliferative syndrome.	Grand EK et al
10688839	2000	FGFR1 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
12393597	2003	Endogenous 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
18205209	2008	The 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
22619110	2012	Identification of a novel partner gene, TPR, fused to FGFR1 in 8p11 myeloproliferative syndrome.	Li F et al
24034896	2013	Inflammatory myofibroblastic tumor with RANBP2 and ALK gene rearrangement: a report of two cases and literature review.	Li J et al
24613277	2014	RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia.	Lim JH et al
12661011	2003	Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor.	Ma Z et al
24307515	2014	inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia that developed in an elderly woman.	Maesako Y et al
11122115	2000	The 8p12 myeloproliferative disorder. t(8;19)(p12;q13.3): a novel translocation involving the FGFR1 gene.	Mugneret F et al
9949182	1999	The 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
20428197	2010	ALK fusion genes in children with atypical myeloproliferative leukemia.	Röttgers S et al
19369959	2009	LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome.	Soler G et al
15800673	2005	The t(8;17)(p11;q23) in the 8p11 myeloproliferative syndrome fuses MYO18A to FGFR1.	Walz C et al
21330321	2011	The 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
9425908	1998	FGFR1 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/favicon/teaching-explorer/