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
(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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https://lup.lub.lu.se/record/1122182
- author
- 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 and Johansson, Bertil LU
- organization
- publishing date
- 2001
- 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}}, }