ArticleNature genetics2015
Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.
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Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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192citing papers in PubMed
24.9field-weighted citation impact, top 1% of its field
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Who cites it
192 citing papers in PubMed, 356 citations in OpenAlex.
- ConstitutionalHaematologica · 2018Trial
- Genomic analysis of germ line and somatic variants in familial myelodysplasia/acute myeloid leukemia.Blood · 2015Trial
- A GermlineEJHaem · 2026Article
- Genetic influences on haematopoiesis.Nature reviews. Genetics · 2026Review
- Article
- Altered cytoskeletal integrity underlies impaired platelet shape change and defective thrombus formation in ETV6-related thrombocytopenia.British journal of haematology · 2026Article
- Importin-9 recognizes the winged-helix fold of ETS transcription factors to mediate nuclear import.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Clinical decisions in clonal hematopoiesis: a contemporary review for clinicians.Haematologica · 2026Review
- Molecular diagnosis of inherited platelet disorder via a targeted whole-exome virtual gene panel: a 5-year institutional experience.Research and practice in thrombosis and haemostasis · 2026Article
- Importins recognize the winged-helix fold of ETS transcription factors to mediate nuclear import.bioRxiv : the preprint server for biology · 2026Article
- Review
- Pediatric leukemia: origins, pathogenesis, the role of microenvironment and immunological modulation.Frontiers in immunology · 2026Review
- Case Report: ETV6 c.744del gene mutation acute lymphoblastic leukemia in identical twins.Frontiers in pediatrics · 2026Article
- How to Read a Next-Generation Sequencing Report for AML and MDS? What Hematologists Need to Know.Journal of clinical medicine · 2025Review
- Observational
- Review
- Familial Patterns in Acute Lymphoblastic Leukemia: Lessons From Three Siblings.Clinical case reports · 2025Article
- Insights into the clinical, platelet and genetic landscape of inherited thrombocytopenia with malignancy risk.British journal of haematology · 2025Article
- A Novel Approach to Prognostic Factors and Risk Stratification in Pediatric AML: Case Report and Literature Review.International journal of molecular sciences · 2025Review
- An unconquered challenge in MDS: review of pathophysiology, clinical manifestations, and management options of MDS with thrombocytopenia.Annals of hematology · 2025Review
132 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 9 institutions in 1 country.
Michael Y ZhangClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Jane E Churpek1] Section of Hematology/Oncology, Center for Clinical Cancer Genetics, University of Chicago, Chicago, Illinois, USA. [2] Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA.
Siobán B KeelDepartment of Medicine, Division of Hematology, University of Washington, Seattle, Washington, USA.
Tom Walsh1] Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA. [2] Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
Ming K Lee1] Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA. [2] Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
Keith R Loeb1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Pathology, University of Washington, Seattle, Washington, USA.
Suleyman Gulsuner1] Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA. [2] Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
Colin C PritchardDepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
Marilyn Sanchez-BonillaClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Jeffrey J DelrowGenomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Ryan S BasomGenomics and Bioinformatics Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.ORCID 0000000161371807
Melissa ForouharPediatric Hematology Oncology, Madigan Army Medical Center, Tacoma, Washington, USA.
Boglarka GyurkoczaClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Bradford S Schwartz1] Morgridge Institute for Research, University of Wisconsin, Madison, Wisconsin, USA. [2] Departments of Medicine and Biomolecular Chemistry, University of Wisconsin, Madison, Wisconsin, USA.
Barbara Neistadt1] Section of Hematology/Oncology, Center for Clinical Cancer Genetics, University of Chicago, Chicago, Illinois, USA. [2] Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA.
Rafael Marquez1] Section of Hematology/Oncology, Center for Clinical Cancer Genetics, University of Chicago, Chicago, Illinois, USA. [2] Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA.
Christopher J Mariani1] Section of Hematology/Oncology, Center for Clinical Cancer Genetics, University of Chicago, Chicago, Illinois, USA. [2] Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA.
Scott A CoatsClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Inga Hofmann1] Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts, USA. [2] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. [3] Harvard Stem Cell Institute, Boston, Massachusetts, USA.
R Coleman Lindsley1] Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
David A Williams1] Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts, USA. [2] Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. [3] Harvard Stem Cell Institute, Boston, Massachusetts, USA.
Janis L AbkowitzDepartment of Medicine, Division of Hematology, University of Washington, Seattle, Washington, USA.
Marshall S HorwitzDepartment of Pathology, University of Washington, Seattle, Washington, USA.
Mary-Claire King1] Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, Washington, USA. [2] Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
Lucy A Godley1] Section of Hematology/Oncology, Center for Clinical Cancer Genetics, University of Chicago, Chicago, Illinois, USA. [2] Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA.
Akiko Shimamura1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Pediatric Hematology/Oncology, Seattle Children's Hospital, Seattle, Washington, USA. [3] Department of Pediatrics, University of Washington, Seattle, Washington, USA.
Fred Hutch Cancer Center · USUniversity of Chicago · USUniversity of Washington · USUniversity of Washington Medical Center · USBoston Children's Hospital · USBrigham and Women's Hospital · USMadigan Army Medical Center · USSeattle Children's Hospital · USUniversity of Wisconsin–Madison · US
Funding
University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4MSPECIFICITY OF OXYGEN DNA DAMAGE AND MUTAGENESISP01AG001751 · NIA · UNIVERSITY OF WASHINGTON · PI RABINOVITCH, PETER S · 1985 to 2021
$29.6MPhysician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1MGENETIC APPROACHES TO AGING RESEARCHT32AG000057 · NIA · UNIVERSITY OF WASHINGTON · PI RABINOVITCH, PETER S · 1985 to 2019
$14.2MRuth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (Parent T32)T32HD007009 · NICHD · UNIVERSITY OF CHICAGO · PI NANCY B SCHWARTZ · 1985 to 2026
$13.0MDeveloping an Oncology Workforce for the 21st Century - Renewal 01K12CA139160 · NCI · UNIVERSITY OF CHICAGO · PI OLOPADE, OLUFUNMILAYO F., SMITH, SONALI · 2010 to 2024
$10.6MTranslational Studies of Inherited Marrow Failure and Myelodysplastic SyndromesR24DK099808 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ABKOWITZ, JANIS L, EBERT, BENJAMIN LEVINE · 2013 to 2017
$8.2MGENOMIC ANALYSIS OF INHERITED BREAST AND OVARIAN CANCERR35CA197458 · NCI · UNIVERSITY OF WASHINGTON · PI KING, MARY-CLAIRE · 2015 to 2021
$6.4MClinical and Molecular Characterization of Familial Marrow Failure SyndromeR24DK093425 · NIDDK · UNIVERSITY OF WASHINGTON · PI ABKOWITZ, JANIS L, KEEL, SIOBAN BRIDGET · 2012 to 2012
$493kNCI NIH HHS K12 CA139160NCI NIH HHS K12CA139160NCI NIH HHS R35 CA197458NCI NIH HHS T32 CA009172NIA NIH HHS P01 AG001751NIA NIH HHS T32 AG000057NIA NIH HHS T32AG000057NICHD NIH HHS T32 HD007009NIDDK NIH HHS R24 DK093425NIDDK NIH HHS R24DK093425NIDDK NIH HHS R24 DK099808NIDDK NIH HHS R24DK099808-01NIGMS NIH HHS T32 GM007266NIGMS NIH HHS T32GM007266
Abstract
We report germline missense mutations in ETV6 segregating with the dominant transmission of thrombocytopenia and hematologic malignancy in three unrelated kindreds, defining a new hereditary syndrome featuring thrombocytopenia with susceptibility to diverse hematologic neoplasms. Two variants, p.Arg369Gln and p.Arg399Cys, reside in the highly conserved ETS DNA-binding domain. The third variant, p.Pro214Leu, lies within the internal linker domain, which regulates DNA binding. These three amino acid sites correspond to hotspots for recurrent somatic mutation in malignancies. Functional studies show that the mutations abrogate DNA binding, alter subcellular localization, decrease transcriptional repression in a dominant-negative fashion and impair hematopoiesis. These familial genetic studies identify a central role for ETV6 in hematopoiesis and malignant transformation. The identification of germline predisposition to cytopenias and cancer informs the diagnosis and medical management of at-risk individuals.
Indexed as
Cell ProliferationETS Translocation Variant 6 ProteinExonsFemaleGenes, ReporterGerm-Line MutationHeLa CellsHematologic NeoplasmsHumansMaleModels, MolecularMolecular Sequence DataMutation, MissensePedigreeProtein Structure, TertiaryProto-Oncogene Proteins c-etsETS Translocation Variant 6 ProteinProto-Oncogene Proteins c-etsRecombinant ProteinsRepressor Proteins
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