t(8;22)(p11;q11) BCR/FGFR1

2002-01-01   Nicholas C P Cross 

1.Department of Molecular and Developmental Biology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan

Clinics and Pathology

Disease

Described in only 3 cases, all of whom had a CML-like (chronic myelogenous leukemia-like) disease. Two had also had an excesss of B-lymphocytes in the marrow.

Phenotype stem cell origin

Involvement of both myeloid and lymphoid cells, so likely to be a stem cell. disorder

Evolution

At the time of writing, one patient had undergone myeloid transformation and a second patient underwent lymphoid transformation followed shortly by myeloid transformation. In common with other patients with FGFR1 fusion genes, the disease therefore appears to be aggressive.

Genes Involved and Proteins

Gene name
FGFR1 (Fibroblast Growth Factor Receptor 1)
Location
8p11.23
Protein description
Receptor tyrosine kinase for FGF ligands, also involved in the t(6;8)(q27;p12), t(8;9)(p12;q32-34) and t(8;13)(p12;q12)
Gene name
BCR (Breakpoint cluster region)
Location
22q11.23
Protein description
Normal function unclear; fuses to ABL in CML .

Result of the Chromosomal Anomaly

Description

5BCR - 3FGFR1

Transcript

All three patients has BCR exon 4 fused to FGFR1 exon 9

Detection protocole

RT-PCR or FISH

Description

Contains the coiled-coil domain of BCR, the BCR Y177 Grb2 binding site and the entire tyrosine kinase domain of FGFR1.

Oncogenesis

Analogous to BCR-ABL: constitutive activation of FGFR1 tyrosine kinase. Transforms Ba/F3 cells to IL-3 independence. Transformed cells are not affected by imatinib (Gleevec/Glivec/STI571) but are inhibited by compounds with anti-FGFR activity.

Bibliography

Pubmed IDLast YearTitleAuthors
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

Summary

Fusion gene

BCR/FGFR1 BCR (22q11.23) FGFR1 (8p11.23) M t(8;22)(p11;q11)|BCR/FGFR1 BCR (22q11.23) FGFR1 (8p11.23) TIC
Atlas Image
it(8;22)(p11;q11) G- banding - Courtesy Jean-Luc Lai (left), Courtesy Diane H Norback, Eric B Johnson, and Sara Morrison-Delap, UW Cytogenetic Services (right).

Citation

Nicholas C P Cross

t(8;22)(p11;q11) BCR/FGFR1

Atlas Genet Cytogenet Oncol Haematol. 2002-01-01

Online version: http://atlasgeneticsoncology.org/haematological/1224/t(8;22)(p11;q11)

External Links