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Identification and functional characterization of imatinib-sensitiveDTD1-PDGFRB and CCDC88C-PDGFRB fusion genes in eosinophilia-associated myeloid/lymphoid neoplasms

Identification and functional characterization of imatinib-sensitiveDTD1-PDGFRB and CCDC88C-PDGFRB fusion genes in eosinophilia-associated myeloid/lymphoid neoplasms
Identification and functional characterization of imatinib-sensitiveDTD1-PDGFRB and CCDC88C-PDGFRB fusion genes in eosinophilia-associated myeloid/lymphoid neoplasms
Eosinophilia-associated myeloid neoplasms with rearrangement of chromosome bands 5q31-33 are frequently associated with PDGFRB fusion genes, which are exquisitely sensitive to treatment with imatinib. In search for novel fusion partners of PDGFRB, we analyzed three cases with translocation t(5;20)(q33;p11), t(5;14)(q33;q32), and t(5;17;14)(q33;q11;q32) by 5?-rapid amplification of cDNA ends polymerase chain reaction (5?-RACE-PCR) and DNA-based long-distance inverse PCR (LDI-PCR) with primers derived from PDGFRB. LDI-PCR revealed a fusion between CCDC88C exon 25 and PDGFRB exon 11 in the case with t(5;17;14)(q33;q11;q32) while 5?-RACE-PCR identified fusions between CCDC88C exon 10 and PDGFRB exon 12 and between DTD1 exon 4 and PDGFRB exon 12 in the cases with t(5;14)(q33;q32) and t(5;20)(q33;p11), respectively. The PDGFRB tyrosine-kinase domain is predicted to be retained in all three fusion proteins. The partner proteins contained coiled-coil domains or other domains, which putatively lead to constitutive activation of the PDGFRB fusion protein. In vitro functional analyses confirmed transforming activity and imatinib-sensitivity of the fusion proteins. All three patients achieved rapid and durable complete hematologic remissions on imatinib.
1098-2264
411-421
Gosenca, Darko
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Kellert, Beate
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Metzgeroth, Georgia
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Haferlach, Claudia
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Fabarius, Alice
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Schwaab, Juliana
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Kneba, Michael
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Scheid, Christof
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Töpelt, Karin
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Erben, Philipp
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Haferlach, Torsten
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Cross, Nicholas C. P.
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Hofmann, Wolf-Karsten
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Seifarth, Wolfgang
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Reiter, Andreas
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Gosenca, Darko
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Kellert, Beate
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Metzgeroth, Georgia
611ec46d-9a11-4e24-ae0f-5ac19dfd0237
Haferlach, Claudia
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Fabarius, Alice
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Schwaab, Juliana
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Kneba, Michael
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Scheid, Christof
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Töpelt, Karin
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Erben, Philipp
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Haferlach, Torsten
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Cross, Nicholas C. P.
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Hofmann, Wolf-Karsten
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Seifarth, Wolfgang
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Reiter, Andreas
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Gosenca, Darko, Kellert, Beate, Metzgeroth, Georgia, Haferlach, Claudia, Fabarius, Alice, Schwaab, Juliana, Kneba, Michael, Scheid, Christof, Töpelt, Karin, Erben, Philipp, Haferlach, Torsten, Cross, Nicholas C. P., Hofmann, Wolf-Karsten, Seifarth, Wolfgang and Reiter, Andreas (2014) Identification and functional characterization of imatinib-sensitiveDTD1-PDGFRB and CCDC88C-PDGFRB fusion genes in eosinophilia-associated myeloid/lymphoid neoplasms. Genes, Chromosomes and Cancer, 53 (5), 411-421. (doi:10.1002/gcc.22153).

Record type: Article

Abstract

Eosinophilia-associated myeloid neoplasms with rearrangement of chromosome bands 5q31-33 are frequently associated with PDGFRB fusion genes, which are exquisitely sensitive to treatment with imatinib. In search for novel fusion partners of PDGFRB, we analyzed three cases with translocation t(5;20)(q33;p11), t(5;14)(q33;q32), and t(5;17;14)(q33;q11;q32) by 5?-rapid amplification of cDNA ends polymerase chain reaction (5?-RACE-PCR) and DNA-based long-distance inverse PCR (LDI-PCR) with primers derived from PDGFRB. LDI-PCR revealed a fusion between CCDC88C exon 25 and PDGFRB exon 11 in the case with t(5;17;14)(q33;q11;q32) while 5?-RACE-PCR identified fusions between CCDC88C exon 10 and PDGFRB exon 12 and between DTD1 exon 4 and PDGFRB exon 12 in the cases with t(5;14)(q33;q32) and t(5;20)(q33;p11), respectively. The PDGFRB tyrosine-kinase domain is predicted to be retained in all three fusion proteins. The partner proteins contained coiled-coil domains or other domains, which putatively lead to constitutive activation of the PDGFRB fusion protein. In vitro functional analyses confirmed transforming activity and imatinib-sensitivity of the fusion proteins. All three patients achieved rapid and durable complete hematologic remissions on imatinib.

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Published date: May 2014
Organisations: Human Development & Health

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Local EPrints ID: 364500
URI: http://eprints.soton.ac.uk/id/eprint/364500
ISSN: 1098-2264
PURE UUID: 50a09003-6414-4698-95dc-18125abe6c82
ORCID for Nicholas C. P. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 01 May 2014 15:43
Last modified: 15 Mar 2024 03:11

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Contributors

Author: Darko Gosenca
Author: Beate Kellert
Author: Georgia Metzgeroth
Author: Claudia Haferlach
Author: Alice Fabarius
Author: Juliana Schwaab
Author: Michael Kneba
Author: Christof Scheid
Author: Karin Töpelt
Author: Philipp Erben
Author: Torsten Haferlach
Author: Wolf-Karsten Hofmann
Author: Wolfgang Seifarth
Author: Andreas Reiter

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