{"doi":"10.1101/2021.11.17.468983","title":"Clonal hematopoiesis in individuals with\n                  <i>ANKRD26</i>\n                  or\n                  <i>ETV6</i>\n                  germline mutations","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Currently, there are at least a dozen recognized hereditary hematopoietic malignancies (HHMs), some of which phenocopy others. Among these, three HHMs driven by germline mutations in\n                  <jats:italic>ANKRD26, ETV6</jats:italic>\n                  , or\n                  <jats:italic>RUNX1</jats:italic>\n                  share a phenotype of thrombocytopenia, qualitative platelet defects, and an increased lifetime risk of hematopoietic malignancies (HMs). Prior work has demonstrated that\n                  <jats:italic>RUNX1</jats:italic>\n                  germline mutation carriers experience an elevated lifetime risk (66%) for developing clonal hematopoiesis (CH) prior to age 50. Germline mutations in\n                  <jats:italic>ANKRD26</jats:italic>\n                  or\n                  <jats:italic>ETV6</jats:italic>\n                  phenocopy\n                  <jats:italic>RUNX1</jats:italic>\n                  germline mutations, but no studies have focused on the risk of CH in individuals with germline mutations in\n                  <jats:italic>ANKRD26</jats:italic>\n                  or\n                  <jats:italic>ETV6</jats:italic>\n                  .\n                </jats:p>\n                <jats:p>\n                  To determine the prevalence of CH in individuals with germline mutations in\n                  <jats:italic>ANKRD26</jats:italic>\n                  or\n                  <jats:italic>ETV6</jats:italic>\n                  , we performed next generation sequencing on hematopoietic tissue from twelve individuals with either germline\n                  <jats:italic>ANKRD26</jats:italic>\n                  or germline\n                  <jats:italic>ETV6</jats:italic>\n                  mutations. Each patient had thrombocytopenia but had not developed HMs. Among the seven individuals with germline\n                  <jats:italic>ANKRD26</jats:italic>\n                  mutations, one patient had a CH clone driven by a somatic\n                  <jats:italic>SF3B1</jats:italic>\n                  mutation (p.Lys700Glu). This mutation increased from a variant allele frequency (VAF) of 9.4% at age 56 to 17.4% at age 60. None of the germline\n                  <jats:italic>ETV6</jats:italic>\n                  mutation carriers had evidence of CH at the limits of detection of the NGS assay (5% VAF). Unlike individuals with germline mutations in\n                  <jats:italic>RUNX1</jats:italic>\n                  , no individuals under the age of 50 with germline mutations in\n                  <jats:italic>ANKRD26</jats:italic>\n                  or\n                  <jats:italic>ETV6</jats:italic>\n                  had detectable CH. This work demonstrates that\n                  <jats:italic>ANKRD26</jats:italic>\n                  germline mutation carriers, but not\n                  <jats:italic>ETV6</jats:italic>\n                  mutation carriers, experience elevated risk for CH.\n                </jats:p>","journal":null,"year":null,"id":24570,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":147043,"name":"Claire C. Homan","orcid":null,"position":1,"is_corresponding":false},{"id":147044,"name":"Kai Yu","orcid":null,"position":2,"is_corresponding":false},{"id":147045,"name":"Marcela Cavalcante de Andrade Silva","orcid":null,"position":3,"is_corresponding":false},{"id":147046,"name":"Kelsey E. McNeely","orcid":null,"position":4,"is_corresponding":false},{"id":147047,"name":"Matthew J. Pozsgai","orcid":null,"position":5,"is_corresponding":false},{"id":147048,"name":"Maria G. Acevedo","orcid":null,"position":6,"is_corresponding":false},{"id":147049,"name":"Jeremy P. Segal","orcid":null,"position":7,"is_corresponding":false},{"id":56540,"name":"Peng Wang","orcid":"0000-0003-1845-7589","position":8,"is_corresponding":false},{"id":147050,"name":"Jinghua Feng","orcid":null,"position":9,"is_corresponding":false},{"id":147051,"name":"Sarah L. King-Smith","orcid":null,"position":10,"is_corresponding":false},{"id":147052,"name":"Erika Kim","orcid":null,"position":11,"is_corresponding":false},{"id":147053,"name":"Sophia C. Korotev","orcid":null,"position":12,"is_corresponding":false},{"id":147054,"name":"David M. Lawrence","orcid":null,"position":13,"is_corresponding":false},{"id":147055,"name":"Andreas W. Schreiber","orcid":null,"position":14,"is_corresponding":false},{"id":147056,"name":"Christopher N. Hahn","orcid":null,"position":15,"is_corresponding":false},{"id":147057,"name":"Hamish S. Scott","orcid":"0000-0002-5813-631X","position":16,"is_corresponding":false},{"id":147058,"name":"Raman Sood","orcid":null,"position":17,"is_corresponding":false},{"id":147059,"name":"Elvira D R P Velloso","orcid":null,"position":19,"is_corresponding":false},{"id":147060,"name":"Anna L. Brown","orcid":null,"position":20,"is_corresponding":false},{"id":147061,"name":"Paul P. Liu","orcid":null,"position":21,"is_corresponding":false},{"id":147062,"name":"Lucy A. Godley","orcid":null,"position":22,"is_corresponding":false},{"id":147042,"name":"Michael W. Drazer","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24523987","pmcid":null,"openalex_id":"https://openalex.org/W3216631139","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"green","license":"cc-by-nc-nd","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/11/22/2021.11.17.468983.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/11/22/2021.11.17.468983.full.pdf","host_type":"GREEN"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2021/11/22/2021.11.17.468983.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2021.11.17.468983","host_type":"publisher"},{"url":"https://doi.org/10.1101/2021.11.17.468983","host_type":"repository"}],"fields_of_study":["Acute Myeloid Leukemia Research","Myeloproliferative Neoplasms: Diagnosis and Treatment","Platelet Disorders and Treatments","Biology","Medicine"],"mesh_terms":[],"keywords":["Germline","Germline mutation","Phenocopy","Germline mosaicism","Biology","Mutation","Genetics","ETV6","Somatic cell","Cancer research","Phenotype","Gene","Chromosomal translocation"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T22:44:18.649542Z","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":[]}