Identification and functional characterization of imatinib‐sensitive DTD1‐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. © 2014 Wiley Periodicals, Inc.