Screening for diverse PDGFRA or PDGFRB by fusion genes is facilitated by generic quantitative RT-PCR

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), 738-744. (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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Contributors

Author: Nicholas C.P. Cross

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