* Interplay between chromosomal alterations and gene mutations shapes the evolutionary trajectory of clonal hematopoiesis.
- 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.
=>1.損害の恐れ, 危険, 冒険, リスク, 2.危険にさらす, 3.敢えてする, 被保険者, 被保険物, 危険にさらす,
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Overview of noun risk
The noun risk has 4 senses (first 2 from tagged texts)
1. (4) hazard, jeopardy, peril, risk, endangerment -- (a source of danger; a possibility of
incurring loss or misfortune; "drinking alcohol is a health hazard")
2. (2) risk, peril, danger -- (a venture undertaken without regard to possible loss or injury; "he
saw the rewards but not the risks of crime"; "there was a danger he would do the wrong thing")
3. risk, risk of infection -- (the probability of becoming infected given that exposure to an
infectious agent has occurred)
4. risk, risk of exposure -- (the probability of being exposed to an infectious agent)
Overview of verb risk
The verb risk has 2 senses (first 2 from tagged texts)
1. (8) risk, put on the line, lay on the line -- (expose to a chance of loss or damage; "We risked
losing a lot of money in this venture"; "Why risk your life?"; "She laid her job on the line when
she told the boss that he was wrong")
2. (2) gamble, chance, risk, hazard, take chances, adventure, run a risk, take a chance -- (take a
risk in the hope of a favorable outcome; "When you buy these stocks you are gambling")
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