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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

Fioretos, Thoas LU ; Panagopoulos, Ioannis LU ; Lassen, Carin LU ; Swedin, Agneta ; Billström, Rolf ; Isaksson, Margareth LU ; Strömbeck, Bodil LU ; Olofsson, Tor LU ; Mitelman, Felix LU orcid and Johansson, Bertil LU (2001) In Genes, Chromosomes and Cancer 32(4). p.302-310
Abstract
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... (More)
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. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Genes, Chromosomes and Cancer
volume
32
issue
4
pages
302 - 310
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:11746971
  • scopus:0035159831
ISSN
1045-2257
DOI
10.1002/gcc.1195
language
English
LU publication?
yes
id
b3d08cfa-1f84-4d9c-b6e4-c368ea00e3a6 (old id 1122182)
date added to LUP
2016-04-01 11:44:10
date last changed
2022-05-14 03:06:09
@article{b3d08cfa-1f84-4d9c-b6e4-c368ea00e3a6,
  abstract     = {{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.}},
  author       = {{Fioretos, Thoas and Panagopoulos, Ioannis and Lassen, Carin and Swedin, Agneta and Billström, Rolf and Isaksson, Margareth and Strömbeck, Bodil and Olofsson, Tor and Mitelman, Felix and Johansson, Bertil}},
  issn         = {{1045-2257}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{302--310}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Genes, Chromosomes and Cancer}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1002/gcc.1195}},
  doi          = {{10.1002/gcc.1195}},
  volume       = {{32}},
  year         = {{2001}},
}