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Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders

Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders
Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders
The BCR–ABL-negative chronic myeloproliferative disorders (CMPD) and myelodysplastic/myeloproliferative diseases (MDS/MPD) are a spectrum of related conditions for which the molecular pathogenesis is poorly understood. Translocations that disrupt and constitutively activate the platelet-derived growth factor receptor ?(PDGFRB) gene at chromosome band 5q33 have been described in some patients, the most common being the t(5;12)(q33;p13). An accurate molecular diagnosis of PDGFRB-rearranged patients has become increasingly important since recent data have indicated that they respond very well to imatinib mesylate therapy. In this study, we have tested nine patients with a CMPD or MDS/MPD and a translocation involving 5q31–33 for disruption of PDGFRB by two-colour fluorescence in situ hybridization (FISH) using differentially labelled, closely flanking probes. Normal control interphase cells gave a false positive rate of 3% (signals more than one signal width apart). Six patients showed a pattern of one fused signal (from the normal allele) and one pair of signals separated by more than one signal width in > 85% of interphase cells, indicating that PDGFRB was disrupted. These individuals had a t(1;5)(q21;q33), t(1;5)(q22;q31), t(1;3;5)(p36;p21;q33), t(2;12;5)(q37;q22;q33), t(3;5) (p21;q31) and t(5;14)(q33;q24) respectively. The remaining three patients with a t(1;5)(q21;q31), t(2;5)(p21;q33) and t(5;6)(q33;q24–25) showed a normal pattern of hybridization, with ? 97% interphase cells with two fusion signals. We conclude that two-colour FISH is useful to determine the presence of a PDGFRB rearrangement, although, as we have shown previously, this technique may not detect subtle complex translocations at this locus. Our data indicate that several PDGFRB partner genes remain to be characterized.
251 - 256
Baxter, E. J.
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Kulkarni, S.
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Vizmanos, J. L.
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Jaju, R.
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Martinelli, G.
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Testoni, N.
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Hughes, G.
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Salamanchuk, Z.
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Calasanz, M. J.
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Lahortiga, I.
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Pocock, C. F.
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Dang, R.
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Fidler, C.
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Wainscoat, J. S.
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Boultwood, J.
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Cross, N. C.
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Baxter, E. J.
4403e524-cfab-4996-98ba-96fd8a960709
Kulkarni, S.
3fedd5b6-a5c6-45b3-bf79-6b950d0d82a1
Vizmanos, J. L.
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Jaju, R.
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Martinelli, G.
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Testoni, N.
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Hughes, G.
d6e5663c-3c56-49f7-b1c5-0cecd97322a3
Salamanchuk, Z.
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Calasanz, M. J.
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Lahortiga, I.
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Pocock, C. F.
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Dang, R.
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Fidler, C.
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Wainscoat, J. S.
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Boultwood, J.
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Cross, N. C.
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Baxter, E. J., Kulkarni, S., Vizmanos, J. L., Jaju, R., Martinelli, G., Testoni, N., Hughes, G., Salamanchuk, Z., Calasanz, M. J., Lahortiga, I., Pocock, C. F., Dang, R., Fidler, C., Wainscoat, J. S., Boultwood, J. and Cross, N. C. (2003) Novel translocations that disrupt the platelet-derived growth factor receptor beta (PDGFRB) gene in BCR-ABL-negative chronic myeloproliferative disorders. British Journal of Haematology, 120 (2), 251 - 256. (doi:10.1046/j.1365-2141.2003.04051.x).

Record type: Article

Abstract

The BCR–ABL-negative chronic myeloproliferative disorders (CMPD) and myelodysplastic/myeloproliferative diseases (MDS/MPD) are a spectrum of related conditions for which the molecular pathogenesis is poorly understood. Translocations that disrupt and constitutively activate the platelet-derived growth factor receptor ?(PDGFRB) gene at chromosome band 5q33 have been described in some patients, the most common being the t(5;12)(q33;p13). An accurate molecular diagnosis of PDGFRB-rearranged patients has become increasingly important since recent data have indicated that they respond very well to imatinib mesylate therapy. In this study, we have tested nine patients with a CMPD or MDS/MPD and a translocation involving 5q31–33 for disruption of PDGFRB by two-colour fluorescence in situ hybridization (FISH) using differentially labelled, closely flanking probes. Normal control interphase cells gave a false positive rate of 3% (signals more than one signal width apart). Six patients showed a pattern of one fused signal (from the normal allele) and one pair of signals separated by more than one signal width in > 85% of interphase cells, indicating that PDGFRB was disrupted. These individuals had a t(1;5)(q21;q33), t(1;5)(q22;q31), t(1;3;5)(p36;p21;q33), t(2;12;5)(q37;q22;q33), t(3;5) (p21;q31) and t(5;14)(q33;q24) respectively. The remaining three patients with a t(1;5)(q21;q31), t(2;5)(p21;q33) and t(5;6)(q33;q24–25) showed a normal pattern of hybridization, with ? 97% interphase cells with two fusion signals. We conclude that two-colour FISH is useful to determine the presence of a PDGFRB rearrangement, although, as we have shown previously, this technique may not detect subtle complex translocations at this locus. Our data indicate that several PDGFRB partner genes remain to be characterized.

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Published date: 2003

Identifiers

Local EPrints ID: 24624
URI: https://eprints.soton.ac.uk/id/eprint/24624
PURE UUID: 4acb585f-ddbd-4c01-904b-4f8cf45fcd57
ORCID for N. C. Cross: ORCID iD orcid.org/0000-0001-5481-2555

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Date deposited: 03 Apr 2006
Last modified: 06 Oct 2018 00:36

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Contributors

Author: E. J. Baxter
Author: S. Kulkarni
Author: J. L. Vizmanos
Author: R. Jaju
Author: G. Martinelli
Author: N. Testoni
Author: G. Hughes
Author: Z. Salamanchuk
Author: M. J. Calasanz
Author: I. Lahortiga
Author: C. F. Pocock
Author: R. Dang
Author: C. Fidler
Author: J. S. Wainscoat
Author: J. Boultwood
Author: N. C. Cross ORCID iD

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