{"doi":"10.1101/2022.09.19.508443","title":"Genomics of PDGFR-rearranged hypereosinophilic syndrome","abstract":"Abstract A subset of patients with hypereosinophilia have a clonal hematologic neoplasm. These neoplastic hypereosinophilic syndromes (HES) can harbor somatic DNA rearrangements involving a PDGF receptor gene, PDGFRA or PGDFRB , most frequently FIP1L1::PDGFRA . Patients with PDGFR - rearranged HES are overwhelmingly males, and the hypereosinophilia responds robustly to the multi-kinase inhibitor imatinib. Unbiased genomics of PDGFR-rearranged HES have not been comprehensively studied. Here, we compared whole genome sequencing of eosinophil DNA from patients with PDGFR-rearranged HES at diagnosis (tumor) versus matched “normal” DNA. Other than the PDGFR rearrangement itself, we detected no recurrent coding somatic point mutations, insertions/deletions, or DNA copy number alterations in the neoplastic eosinophils; instead, there were additional somatic events private to each tumor. The tumors had a linear clonal structure with the PDGFR rearrangement as the initial driver event. We mapped the breakpoints of a novel IQGAP2::PDGFRB::UVRAG intra- and inter-chromosomal fusion event in one patient. Non-coding analysis found no recurrent abnormalities, including in eosinophilic leukemia-associated promoters or enhancers. The sex chromosomes showed no recurrent alterations to provide an obvious explanation for the disease’s extreme male bias. We conclude that neoplastic HES has relatively simple genomics and that the only unambiguous recurrent driver event is the PDGFR rearrangement itself. Key Points PDGFR-rearranged hypereosinophilic neoplasms have simple, linear genetic structure with the rearrangement as the likely initiating event There are no obvious recurrent additional or sex-biased genomic events that cooperate with PDGFR rearrangement to drive the neoplasm","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":304319,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":997138,"name":"Meifang Qi","orcid":"0000-0002-8671-3110","position":1,"is_corresponding":false},{"id":997139,"name":"Juliette Bouyssou","orcid":"0000-0002-2301-0426","position":2,"is_corresponding":false},{"id":104191,"name":"Andrew J. Oler","orcid":"0000-0002-6310-0434","position":3,"is_corresponding":false},{"id":365523,"name":"Lauren Thumm","orcid":null,"position":4,"is_corresponding":false},{"id":368830,"name":"Michelle Makiya","orcid":"0000-0002-5673-3815","position":5,"is_corresponding":false},{"id":280055,"name":"Irina Marić","orcid":null,"position":6,"is_corresponding":false},{"id":237529,"name":"Amy D. Klion","orcid":"0000-0002-4986-5326","position":7,"is_corresponding":false},{"id":75579,"name":"Andrew A. Lane","orcid":"0000-0001-7380-0226","position":8,"is_corresponding":false},{"id":267579,"name":"Esther Rheinbay","orcid":"0000-0002-5566-6729","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T00:32:32.651796Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}