The t(6;8)(q27;p11) translocation in a stem cell myeloproliferative disorder fuses a novel gene, FOP, to fibroblast growth factor receptor 1

In patients with an atypical stem-cell myeloproliferative disorder with lym phoma (B or T cell), myeloid hyperplasia, and eosinophilia, the chromosome 8p11-12 region is the site of a recurrent breakpoint that can be associated with three different partners, 6q27, 9q32-34, and 13q12. Rearrangements ar e supposed to affect a pluripotent stem cell capable of myeloid and lymphoi d differentiation and to involve the same 8p11-12 gene. The t(8;13) translo cation has recently been shown to result in a fusion between the FGFR1 gene that encodes a tyrosine kinase receptor for fibroblast growth factors and a novel gene, FIM (also called RAMP or ZNF198), belonging to a novel family of zinc finger genes. In the present study, we have cloned the t(6;8)(q27; pll) translocation in two patients and found a fusion between FGFR1 and a n ovel gene, FOP (FGFR1 Oncogene Partner), located on chromosome band 6q27, T his gene is alternatively spliced and ubiquitously expressed. It encodes a protein containing two regions of putative leucine-rich repeats putatively folding in alpha-helices and separated by a hydrophobic spacer. The two rec iprocal fusion transcripts were evidenced by reverse transcription-polymera se chain reaction in the tumoral cells of the patients. The predicted chime ric FOP-FGFR1 protein contains the FOP N-terminus leucine-rich region fused to the catalytic domain of FGFR1. It may promote hematopoietic stem cell p roliferation and leukemogenesis through a constitutive phosphorylation and activation of the downstream pathway of FGFR1. (C) 1999 by The American Soc iety of Hematology.