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

Autor:	Mack T; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee., Vlasschaert C; Department of Medicine, Queen's University, Kingston, Ontario, Canada., von Beck K; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Silver AJ; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee., Heimlich JB; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Poisner H; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee., Condon HR; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee., Ulloa J; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee., Sochacki AL; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Spaulding TP; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Kishtagari A; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee., Bejan CA; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee., Xu Y; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee., Savona MR; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee; Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Immunobiology, Vanderbilt University Medical Center, Nashville, Tennessee., Jones A; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee., Bick AG; Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, Tennessee; Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: alexander.bick@vumc.org.
Jazyk:	angličtina
Zdroj:	The Journal of molecular diagnostics : JMD [J Mol Diagn] 2024 Jul; Vol. 26 (7), pp. 563-573. Date of Electronic Publication: 2024 Apr 06.
DOI:	10.1016/j.jmoldx.2024.03.007
Abstrakt:	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. Competing Interests: Disclosure Statement M.R.S. has received honoraria for advisory board membership or consultancy from Bristol Myers Squibb, CTI, Forma, Geron, GlaxoSmithKline/Sierra Oncology, Karyopharm, Ryvu Therapeutics, and Taiho Pharmaceutical; has received research funding from ALX Oncology, Astex Pharmaceuticals, Incyte Corporation, Takeda, and TG Therapeutics; holds equity in Empath Biosciences, Karyopharm, and Ryvu Therapeutics; and has been reimbursed for travel expenses by Astex. A.G.B. has received honoraria for advisory board membership from, and holds equity in, TenSixteen Bio. (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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