在癌症的背景下，不确定潜力的克隆性造血干细胞病变（CHIP）与治疗相关的髓样新生物的发展以及更短的总体生存有关。细胞外DNA（cfDNA）测序正广泛用于对癌症患者进行基因组筛查，但由于需要匹配的血液和肿瘤测序，因此尚未广泛用于确定CHIP状态。我们提出了一种准确的分类方法，可以仅通过cfDNA测序确定CHIP状态，并将我们的模型应用于4324个肿瘤临床cfDNA样本。使用此方法，我们确定了此队列中30.3％的患者具有CH证据，并且CH的发生率因肿瘤类型而异。匹配的RNA测序数据显示，患有CH的患者的肿瘤和肿瘤微环境中存在明显的炎症，尤其是中性粒细胞激活。此外，患有CH的患者有全身性中性粒细胞激活的证据，这指向与CH状态相关的更糟糕结果的可能机制。中性粒细胞激活可能是许多机制之一，因为携带TET2框移突变的雌激素受体阳性乳腺癌患者具有类似的中性粒细胞频率，但具有更糟糕的结果。这些数据表明，仅通过cfDNA测序就可以检测出CH的可行性，并应用此方法，证明患有CH的患者在全身和肿瘤微环境中均具有增加的炎症。

In the context of cancer, clonal hematopoiesis of indeterminate potential (CHIP) is associated with the development of therapy-related myeloid neoplasms and shorter overall survival. Cell-free DNA (cfDNA) sequencing is becoming widely adopted for genomic screening of patients with cancer but has not been used extensively to determine CHIP status because of a requirement for matched blood and tumor sequencing. We present an accurate classification approach to determine the CH status from cfDNA sequencing alone, applying our model to 4324 oncology clinical cfDNA samples. Using this method, we determined that 30.3% of patients in this cohort have evidence of CH, and the incidence of CH varies by tumor type. Matched RNA sequencing data show evidence of increased inflammation, especially neutrophil activation, within the tumors and tumor microenvironments of patients with CH. In addition, patients with CH had evidence of neutrophil activation systemically, pointing to a potential mechanism of action for the worse outcomes associated with CH status. Neutrophil activation may be one of many mechanisms, however, because patients with estrogen receptor-positive breast cancer harboring TET2 frameshift mutations had worse outcomes but similar neutrophil frequencies to patients without CH. Together, these data show the feasibility of detecting CH through cfDNA sequencing alone and an application of this method, demonstrating increased inflammation in patients with CH both systemically and in the tumor microenvironment.