Nanopore Sequencing for the screening of Myeloid and Lymphoid neoplasms with eosinophilia and rearrangement of PDGFRa, PDGFRb, FGFR1 or PCM1-JAK2.

Primary Eosinophilic Disorders (PED) represent a group of diseases with heterogeneous pathophysiology and diversified clinical phenotypes. Among the clonal alterations found in PED, gene fusions involving PDGFR?, PDGFR?, FGFR1 or JAK2 cluster in the WHO category of myeloid and lymphoid neoplasms with eosinophilia. The heterogeneous nature of genomic aberrations and the promiscuity of fusion partners, may limit the diagnostic accuracy of conventional cytogenetic approaches. To address such technical challenges, we exploited a nanopore-based sequencing platform to screen a cohort of patients referred for the characterization of a PED. We show that nanopore sequencing enables fast (within 60 hours) and precise identification of genomic fusion events, starting from whole blood DNA. Overall design: We report the application of Oxford Nanopore sequencing technology for the identification of gene fusions involving PDGFRa, PDGFRb, FGFR1 and JAK2