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.

Bibliography

Pubmed ID	Last Year	Title	Authors

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/deep-insight-explorer/