AI Article Synopsis
- - The study investigates clonal hematopoiesis (CH) in cancer patients and its link to an increased leukemia risk, using blood sequencing data from over 32,000 patients to analyze gene mutations and chromosomal alterations simultaneously.
- - Findings reveal that certain genetic combinations account for 23% of observed alterations in CH, indicating that these genetic changes occur early in the evolution toward potential leukemia.
- - The research highlights that chromosomal alterations are significant independent risk factors for leukemia development, suggesting that both gene mutations and chromosomal changes should be monitored in patients at risk.
Article Abstract
Stably acquired mutations in hematopoietic cells represent substrates of selection that may lead to clonal hematopoiesis (CH), a common state in cancer patients that is associated with a heightened risk of leukemia development. Owing to technical and sample size limitations, most CH studies have characterized gene mutations or mosaic chromosomal alterations (mCAs) individually. Here we leverage peripheral blood sequencing data from 32,442 cancer patients to jointly characterize gene mutations (n = 14,789) and mCAs (n = 383) in CH. Recurrent composite genotypes resembling known genetic interactions in leukemia genomes underlie 23% of all detected autosomal alterations, indicating that these selection mechanisms are operative early in clonal evolution. CH with composite genotypes defines a patient group at high risk of leukemia progression (3-year cumulative incidence 14.6%, CI: 7-22%). Multivariable analysis identifies mCA as an independent risk factor for leukemia development (HR = 14, 95% CI: 6-33, P < 0.001). Our results suggest that mCA should be considered in conjunction with gene mutations in the surveillance of patients at risk of hematologic neoplasms.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804935 | PMC |
| http://dx.doi.org/10.1038/s41467-020-20565-7 | DOI Listing |
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