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.

Article Bibliography

Pubmed IDLast YearTitleAuthors

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/js/gene-explorer/