Related Experiment Video
Updated: Apr 20, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
The diversity of mutations and clinical outcomes for ELANE-associated neutropenia
Vahagn Makaryan1, Cornelia Zeidler, Audrey Anna Bolyard
1aDepartment of Medicine, University of Washington, Seattle, USA bDepartment of Molecular Hematopoiesis, Kinderklinik, MedizinischeHochschule, Hannover cInternal Medicine II, University Hospital, Tübingen, Tübingen, Germany dDepartment of Medicine, University of Washington, Severe Chronic Neutropenia International Registry, Seattle ePediatric Hematology Oncology, University of Michigan, Ann Arbor fPediatric Hematology Oncology, Saint Joseph's Children's Hospital, Paterson gDepartments of Pediatrics and Cancer Biology, University of Massachusetts Medical School, Worcester hPediatric Hematology/Oncology, Fred Hutchinson Cancer Research Center, Seattle iBiostatistics Branch, National Cancer Institute at the National Institutes of Health, Division of Cancer Epidemiology & Genetics, Bethesda jDivision of Oncology, Washington University, St Louis, USA *Vahagn Makaryan and Cornelia Zeidler contributed equally to the writing of this article.
Purpose Of Review:
Mutations in the gene for neutrophil elastase, ELANE, cause cyclic neutropenia (CyN) and severe congenital neutropenia (SCN). This study summarized data from the Severe Chronic Neutropenia International Registry (SCNIR) on genotype-phenotype relationships of ELANE mutations to important clinical outcomes. We also summarize findings for ELANE mutations not observed in SCNIR patients.
Recent Findings:
There were 307 SCNIR patients with 104 distinctive ELANE mutations who were followed longitudinally for up to 27 years. The ELANE mutations were diverse; there were 65 single amino acid substitutions; 61 of these mutations (94%) were 'probably' or 'possibly damaging' by PolyPhen-2 analysis, and one of the 'benign' mutations was associated with two cases of acute myeloid leukemia (AML). All frame-shift mutations (19/19) were associated with the SCN. The pattern of mutations in the SCN versus CyN was significantly different (P < 10), but some mutations were observed in both groups (overlapping mutations). The cumulative incidence of severe adverse events, that is, myelodysplasia, AML, stem cell transplantation, or deaths was significantly greater for patients with SCN versus those with CyN or overlapping mutations. Specific mutations (i.e. G214R or C151Y) had a high risk for evolution to AML.
Summary:
Sequencing is useful for predicting outcomes of ELANE-associated neutropenia.
Related Concept Videos
Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
Mutations in Microorganisms
Spontaneous and Induced Mutations
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...

