Mutated clones in healthy tissues may hold clues for the earlier detection of malignancy Over time, somatic mutations accrue during normal cell division and tissue self-renewal. The patterns of age-associated somatic mutation have been perhaps most extensively characterized in the blood. Although many mutations are functionally benign, a subset represents premalignant initiating events in hematopoietic stem cells that result in clonal expansion. This clonal hematopoiesis confers an increased risk of hematologic malignancy (after the accrual of additional cooperating mutations), as well as cardiovascular disease and overall mortality (1). On page 1449 of this issue, Watson et al. (2) investigate the clonal architecture and evolutionary dynamics of healthy blood by analyzing targeted DNA sequences of ∼50,000 blood cancer–free individuals. They find that positive selection for beneficial mutations, rather than neutral genetic drift, dictates the genetic diversity of normal blood. The identification of mutant clones and their associated fitness benefits could improve disease risk stratification.

中文翻译：

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量化健康血液中的突变

健康组织中的突变克隆可能为早期发现恶性肿瘤提供线索 随着时间的推移，体细胞突变会在正常细胞分裂和组织自我更新过程中产生。与年龄相关的体细胞突变模式可能在血液中得到了最广泛的表征。尽管许多突变在功能上是良性的，但一个子集代表了造血干细胞中导致克隆扩增的癌前起始事件。这种克隆性造血增加了恶性血液病的风险（在额外的合作突变发生后），以及心血管疾病和总体死亡率 (1)。在本期第 1449 页上，Watson 等人。(2) 通过分析约 50,000 名无血癌个体的靶向 DNA 序列，研究健康血液的克隆结构和进化动力学。他们发现对有益突变的积极选择，而不是中性遗传漂变，决定了正常血液的遗传多样性。突变克隆的鉴定及其相关的适应性益处可以改善疾病风险分层。