Cost-Effective and Scalable Clonal Hematopoiesis Assay Provides Insight into Clonal Dynamics

Details

• Personal Author:
  Bejan CA ; Bick AG ; Condon HR ; Heimlich JB ; Jones A ; Kishtagari A ; Mack T ; Poisner H ; Savona MR ; Silver AJ ; Sochacki AL ; Spaulding TP ; Ulloa J ; Vlasschaert C ; von Beck K ; Xu Y
• Description:
  Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related phenomenon in which hematopoietic stem cells acquire mutations in a select set of genes commonly mutated in myeloid neoplasia which then expand clonally. Current sequencing assays to detect CHIP mutations are not optimized for the detection of these variants and can be cost-prohibitive when applied to large cohorts or to serial sequencing. In this study, an affordable (approximately US $8 per sample), accurate, and scalable sequencing assay for CHIP is introduced and validated. The efficacy of the assay was demonstrated by identifying CHIP mutations in a cohort of 456 individuals with DNA collected at multiple time points in Vanderbilt University's biobank and quantifying clonal expansion rates over time. A total of 101 individuals with CHIP/clonal cytopenia of undetermined significance were identified, and individual-level clonal expansion rate was calculated using the variant allele fraction at both time points. Differences in clonal expansion rate by driver gene were observed, but there was also significant individual-level heterogeneity, emphasizing the multifactorial nature of clonal expansion. Additionally, mutation co-occurrence and clonal competition between multiple driver mutations were explored. [Description provided by NIOSH]
• Subjects:
  Blood Diagnosis Genetics Hematologic Tests Occupational Health Safety
• Keywords:
  Blood Cells Diagnostic Tests Genes Hematology Hematopoiesis Myeloid Tissue
• ISSN:
  1525-1578
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2 ; OSHA Region 4 ; Tennessee
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  26
• Issue:
  7
• NIOSHTIC Number:
  nn:20070832
• Citation:
  J Mol Diagn 2024 Jul; 26(7):563-573
• Contact Point Address:
  Alexander G. Bick, M.D., Ph.D., Vanderbilt University Medical Center, 550 Robinson Research Bldg., 2200 Pierce Ave., Nashville, TN 37232
• Email:
  alexander.bick@vumc.org
• Federal Fiscal Year:
  2024
• Performing Organization:
  Albert Einstein College of Medicine, Bronx, New York
• Peer Reviewed:
  True
• Start Date:
  20210701
• Source Full Name:
  The Journal of Molecular Diagnostics
• End Date:
  20240630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f17d43181e6b8d7b3916112f955b4543f59f8a98c606369fcbbe8f1959336bb19f01fd2b40e159dd849e886a2951399251dde182a4b55063d5caacf7e563a56f
• Download URL:
  https://stacks.cdc.gov/view/cdc/208980/cdc_208980_DS1.pdf
• File Type:
  [PDF - 1.91 MB ]