Longitudinal profiling of clonal hematopoiesis provides insight into clonal dynamics.
Citation: Immunity & Ageing [Electronic Resource]: I & A. 19(1):23, 2022 May 24.PMID: 35610705Institution: MedStar Heart & Vascular InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleYear: 2022Local holdings: Available online through MWHC library: 2004 - presentISSN:- 1742-4933
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
---|---|---|---|---|---|---|
Journal Article | MedStar Authors Catalog | Article | 35610705 | Available | 35610705 |
Available online through MWHC library: 2004 - present
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of mutant hematopoietic stem cells, confers risk for multiple diseases of aging including hematologic cancer and cardiovascular disease. Whole-exome or genome sequencing can detect CHIP, but due to those assays' high cost, most population studies have been cross-sectional, sequencing only a single timepoint per individual.
CONCLUSIONS: Targeted smMIPS sequencing can sensitively measure clonal dynamics in CHIP. Mutations that reached the conventional threshold for CHIP (2% frequency) tended to continue growing, indicating that after CHIP is acquired, it is generally not lost. The ability to cost-effectively profile CHIP longitudinally will enable future studies to investigate why some CHIP clones expand, and how their dynamics relate to health outcomes at a biobank scale. Copyright © 2022. The Author(s).
RESULTS: We developed and validated a cost-effective single molecule molecular inversion probe sequencing (smMIPS) assay for detecting CHIP, targeting the 11 most frequently mutated genes in CHIP along with 4 recurrent mutational hotspots. We sequenced 548 multi-timepoint samples collected from 182 participants in the Women's Health Initiative cohort, across a median span of 16 years. We detected 178 driver mutations reaching variant allele frequency >= 2% in at least one timepoint, many of which were detectable well below this threshold at earlier timepoints. The majority of clonal mutations (52.1%) expanded over time (with a median doubling period of 7.43 years), with the others remaining static or decreasing in size in the absence of any cytotoxic therapy.
English