Premium
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
Author(s) -
Fioretos Thoas,
Panagopoulos Ioannis,
Lassen Carin,
Swedin Agneta,
Billström Rolf,
Isaksson Margareth,
Strömbeck Bodil,
Olofsson Tor,
Mitelman Felix,
Johansson Bertil
Publication year - 2001
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.1195
Subject(s) - fusion gene , fibroblast growth factor receptor 1 , breakpoint cluster region , biology , tyrosine kinase , fibroblast growth factor receptor , cancer research , fusion protein , abl , receptor tyrosine kinase , exon , microbiology and biotechnology , chromosomal translocation , gene , genetics , fibroblast growth factor , receptor , recombinant dna
Constitutive activation of tyrosine kinases as a consequence of chromosomal translocations, forming fusion genes, plays an important role in the development of hematologic malignancies, in particular, myeloproliferative syndromes (MPSs). In this respect, the t(9;22)(q34;q11) that results in the BCR/ABL fusion gene in chronic myeloid leukemia is one of the best‐studied examples. The fibroblast growth factor receptor 1 ( FGFR1 ) gene at 8p11 encodes a transmembrane receptor tyrosine kinase and is similarly activated by chromosomal translocations, in which three alternative genes— ZNF198 at 13q12, CEP110 at 9q34, and FOP at 6q27—become fused to the tyrosine kinase domain of FGFR1 . These 8p11‐translocations are associated with characteristic morphologic and clinical features, referred to as “8p11 MPS.” In this study, we report the isolation and characterization of a novel fusion gene in a hematologic malignancy with a t(8;22)(p11;q11) and features suggestive of 8p11 MPS. We show that the breakpoints in the t(8;22) occur within introns 4 and 8 of the BCR and FGFR1 genes, respectively. On the mRNA level, the t(8;22) results in the fusion of BCR exons 1–4 in‐frame with the tyrosine kinase domain of FGFR1 as well as in the expression of a reciprocal FGFR1/BCR chimeric transcript. By analogy with data obtained from previously characterized fusion genes involving FGFR1 and BCR/ABL , it is likely that the oligomerization domain contributed by BCR is critical and that its dimerizing properties lead to aberrant FGFR1 signaling and neoplastic transformation. © 2001 Wiley‐Liss, Inc.