高风险的克隆性造血干细胞(Clonal Hematopoiesis, CH)在进行血浆无细胞DNA测序的实体肿瘤患者中常常被意外发现。因此，我们的研究目的是探讨如果利用液体活检意外检测到高风险 CH 是否能够揭示实体肿瘤患者的隐匿血液恶性肿瘤。在贡塞夫·鲁西癌症分型研究项目( ClinicalTrials.gov标识符: NCT04932525)中，我们招募了患有晚期实体癌的成年患者，并进行至少一次液体活检测试 (FoundationOne Liquid CDx)。分子学报告在贡塞夫·鲁西分子肿瘤委员会 (MTB) 中讨论。在 JAK2、MPL 或 MYD88 的致病性突变中，暴露的 CH 变异都将触发血液学咨询，而与变异等位基因频率(VAF)无关；当 DNMT3A、TET2、ASXL1、IDH1、IDH2、SF3B1 或 U2AF1 的 VAF 大于等于 10% 时，也将考虑患者癌症相关预后。目前文献中对于 TP53 突变还没有公认的分类方法，因此每个病例都会进行讨论。 研究时间为 2021 年 3 月至 10 月，共收集了 1,416 例患者。发现 110 例患者(占总样本比例的 7.7%)携带至少一种高风险 CH 突变：DNMT3A(n=32)、JAK2(n=28)、TET2(n=19)、ASXL1(n=18)、SF3B1(n=5)、IDH1(n=4)、IDH2(n=3)、MPL(n=3) 和 U2AF1(n=2)。在 MTB 的建议下，对其中的 45 例患者进行了血液学咨询。总体而言，实际上有 18 例患者接受了咨询，其中 9 例患者确诊了隐匿的血液恶性肿瘤：2 例患者患有骨髓增生异常综合征，2例实质性血小板增多症，1例边缘区淋巴瘤和1例 Waldenström 巨球蛋白血症。其余的 3 例患者已经在血液学方面接受了随访治疗。 液体活检的意外发现可能会引发诊断性的血液学检查，并揭示出隐匿的恶性血液肿瘤，在对患者进行多学科的情况分析后，需要进行个别化的治疗方案讨论。

High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell-free DNA sequencing. Here, we aimed to determine if the incidental detection of high-risk CH by liquid biopsy may reveal occult hematologic malignancies in patients with solid tumors.Adult patients with advanced solid cancers enrolled in the Gustave Roussy Cancer Profiling study (ClinicalTrials.gov identifier: NCT04932525) underwent at least one liquid biopsy (FoundationOne Liquid CDx). Molecular reports were discussed within the Gustave Roussy Molecular Tumor Board (MTB). Potential CH alterations were observed, and patients referred to hematology consultation in the case of pathogenic mutations in JAK2, MPL, or MYD88, irrespective of the variant allele frequency (VAF), or in DNMT3A, TET2, ASXL1, IDH1, IDH2, SF3B1, or U2AF1 with VAF ≥ 10%, while also considering patient cancer-related prognosis. TP53 mutations were discussed case-by-case.Between March and October 2021, 1,416 patients were included. One hundred ten patients (7.7%) carried at least one high-risk CH mutation: DNMT3A (n = 32), JAK2 (n = 28), TET2 (n = 19), ASXL1 (n = 18), SF3B1 (n = 5), IDH1 (n = 4), IDH2 (n = 3), MPL (n = 3), and U2AF1 (n = 2). The MTB advised for hematologic consultation in 45 patients. Overall, 9 patients of 18 actually addressed had confirmed hematologic malignancies that were occult in six patients: two patients had myelodysplastic syndrome, two essential thrombocythemia, one a marginal lymphoma, and one a Waldenström macroglobulinemia. The other three patients were already followed up in hematology.The incidental findings of high-risk CH through liquid biopsy may trigger diagnostic hematologic tests and reveal an occult hematologic malignancy. Patients should have a multidisciplinary case-by-case evaluation.