Screening for diverse PDGFRA or PDGFRB by fusion genes is facilitated by generic quantitative RT-PCR
Screening for diverse PDGFRA or PDGFRB by fusion genes is facilitated by generic quantitative RT-PCR
Backround: rapid identification of diverse fusion genes with involvement of PDGFRA or PDGFRB in eosinophilia-associated myeloproliferative neoplasms (Eos-MPN) is essential for adequate clinical management but is complicated by the multitude and heterogeneity of partner genes and breakpoints. Design and Methods. We established generic quantitative RT-PCR assays (RQ-PCR) to detect overexpression of 3'-regions of PDGFRA or PDGFRB as a possible indicator of an underlying fusion.
Results: at diagnosis, all patients with known fusion genes involving PDGFRA (n=5, 51 patients) or PDGFRB (n=5; 7 patients) showed significantly increased normalized expression levels compared to 191 patients with fusion gene-negative eosinophilia or healthy individuals (PDGFRA/ABL: 0.73 vs. 0.0066 vs. 0.0064, p<0.0001; PDGFRB/ABL: 196 vs. 3.8 vs. 5.85, p<0.0001). Sensitivity and specificity of the activation screening test is 100% and 88.4% for PDGFRA and 100% and 94% for PDGFRB, respectively. Furthermore, significant overexpression of PDGFRB was found in an Eos-MPN patient with uninformative cytogenetics and excellent response to imatinib. Subsequently, a new SART3-PDGFRB fusion gene was identified by 5'-RACE-PCR.
Conclusion: RQ-PCR is a simple and useful adjunct standard diagnostic assays to detect clinically significant overexpression of PDGFRA and PDGFRB in Eos-MPNs or related disorders
MPN, PDGFRA, PDGFRB, RQ-PCR
738-744
Erben, Philipp
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Gosenca, Darko
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Muller, Martin C.
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Reinhard, Jelena
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Score, Joannah
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del Valle, Francesco
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Walz, Chistoph
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Mix, Jurgen
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Metzgeroth, Georgia
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Ernst, Thomas
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Haferlach, Claudia
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Cross, Nicholas C.P.
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Hochhaus, Andreas
b37b9b7d-85ff-455e-994d-fcc2adf94088
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede
27 May 2010
Erben, Philipp
defa0bda-e318-499b-9f62-36288a8407ae
Gosenca, Darko
0a32fea9-fcac-4e5c-83a3-65c8e99ea704
Muller, Martin C.
34ec2215-e464-4320-a867-cc64a6b3dc38
Reinhard, Jelena
d4f30272-305f-43b1-9efb-0444cbd6bfff
Score, Joannah
ea0db6ef-c17e-4915-b216-ac67c07b26b7
del Valle, Francesco
17b613be-c68f-4dbc-8ab0-6310eff831a6
Walz, Chistoph
d37b058b-dd3f-4ee1-a15f-6178dffb6471
Mix, Jurgen
3fd9c7c7-4844-4625-9c73-baf13a30d6a1
Metzgeroth, Georgia
611ec46d-9a11-4e24-ae0f-5ac19dfd0237
Ernst, Thomas
96c7805b-c900-4545-9f93-1a83d789cb56
Haferlach, Claudia
0bf0896a-7b9c-451a-9e64-935ecdd7aa15
Cross, Nicholas C.P.
f87650da-b908-4a34-b31b-d62c5f186fe4
Hochhaus, Andreas
b37b9b7d-85ff-455e-994d-fcc2adf94088
Reiter, Andreas
ffa23e84-4a13-4cb5-aaf0-3fafe25dbede
Erben, Philipp, Gosenca, Darko, Muller, Martin C., Reinhard, Jelena, Score, Joannah, del Valle, Francesco, Walz, Chistoph, Mix, Jurgen, Metzgeroth, Georgia, Ernst, Thomas, Haferlach, Claudia, Cross, Nicholas C.P., Hochhaus, Andreas and Reiter, Andreas
(2010)
Screening for diverse PDGFRA or PDGFRB by fusion genes is facilitated by generic quantitative RT-PCR.
Haematologica, 95 (5), .
(doi:10.3324/haematol.2009.016345).
Abstract
Backround: rapid identification of diverse fusion genes with involvement of PDGFRA or PDGFRB in eosinophilia-associated myeloproliferative neoplasms (Eos-MPN) is essential for adequate clinical management but is complicated by the multitude and heterogeneity of partner genes and breakpoints. Design and Methods. We established generic quantitative RT-PCR assays (RQ-PCR) to detect overexpression of 3'-regions of PDGFRA or PDGFRB as a possible indicator of an underlying fusion.
Results: at diagnosis, all patients with known fusion genes involving PDGFRA (n=5, 51 patients) or PDGFRB (n=5; 7 patients) showed significantly increased normalized expression levels compared to 191 patients with fusion gene-negative eosinophilia or healthy individuals (PDGFRA/ABL: 0.73 vs. 0.0066 vs. 0.0064, p<0.0001; PDGFRB/ABL: 196 vs. 3.8 vs. 5.85, p<0.0001). Sensitivity and specificity of the activation screening test is 100% and 88.4% for PDGFRA and 100% and 94% for PDGFRB, respectively. Furthermore, significant overexpression of PDGFRB was found in an Eos-MPN patient with uninformative cytogenetics and excellent response to imatinib. Subsequently, a new SART3-PDGFRB fusion gene was identified by 5'-RACE-PCR.
Conclusion: RQ-PCR is a simple and useful adjunct standard diagnostic assays to detect clinically significant overexpression of PDGFRA and PDGFRB in Eos-MPNs or related disorders
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Published date: 27 May 2010
Keywords:
MPN, PDGFRA, PDGFRB, RQ-PCR
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Local EPrints ID: 72203
URI: http://eprints.soton.ac.uk/id/eprint/72203
ISSN: 0390-6078
PURE UUID: 59894331-0b20-4340-b65f-92e553fd26ee
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Date deposited: 01 Feb 2010
Last modified: 14 Mar 2024 02:46
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Contributors
Author:
Philipp Erben
Author:
Darko Gosenca
Author:
Martin C. Muller
Author:
Jelena Reinhard
Author:
Joannah Score
Author:
Francesco del Valle
Author:
Chistoph Walz
Author:
Jurgen Mix
Author:
Georgia Metzgeroth
Author:
Thomas Ernst
Author:
Claudia Haferlach
Author:
Andreas Hochhaus
Author:
Andreas Reiter
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