Untangling the Relationship Between Clonal Hematopoiesis and Ovarian Cancer Therapies.
Untangling the Relationship Between Clonal Hematopoiesis and Ovarian Cancer Therapies.
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阐明克隆造血与卵巢癌治疗之间的关系。
DOI：
10.1093/jnci/djab234
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Takahashi,Koichi
中科院分区：
文献类型：
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作者：
Takahashi,Koichi
从历史上看，克隆造血（CH）和卵巢癌之间有着牢不可破的联系。血液中的镶嵌PPM 1D突变首先在乳腺癌和卵巢癌患者中发现（1）。人们认为，血液中的镶嵌PPM 1D突变是乳腺癌和卵巢癌遗传易感性的一种新形式。后来我们才明白，这是一种在接受化疗的卵巢癌患者中富集的CH形式。在本期杂志中，Weber-Lassalle及其同事分析了从参加AGO-TR 1观察性试验的卵巢癌患者中收集的血液样本。该研究包括448例卵巢癌患者，其生殖系BRCA 1和2（gBRCA 1/2）状态已被裁定。他们覆盖了10个与CH相关的基因（ASXL 1，DNMT 3A，GNAS，JAK 2，PPM 1D，SF 3B 1，SH 2B 3，SRSF 2，TET 2和TP 53），在17.6%的患者中检测到CH。毫不奇怪，CH与抽血时的较高年龄和既往化疗史相关。此外，几乎仅在接受至少一线铂类化疗的患者中发现了PPM 1D和TP 53突变的CH。这与临床前研究结果一致，即铂类化疗促进了具有DNA损伤途径突变（PPM 1D和TP 53）的CH的阳性选择（3，4）。
Historically, there is an unbreakable tie between clonal hematopoiesis (CH) and ovarian cancer. Mosaic PPM1D mutations in blood were first identified in patients with breast and ovarian cancers (1). It was believed that the mosaic PPM1D mutation in blood was a novel form of the genetic predisposition for breast and ovarian cancers. It was only later that we understood that this was a form of CH enriched in ovarian cancer patients exposed to chemotherapy treatment. In this issue of the Journal, Weber-Lassalle and colleagues (2) analyzed blood samples collected from patients with ovarian cancer enrolled in the AGO-TR1 observational trial. The study consisted of 448 patients with ovarian cancer whose germline BRCA1 and 2 (gBRCA1/2) status was adjudicated. Covering 10 genes associated with CH (ASXL1, DNMT3A, GNAS, JAK2, PPM1D, SF3B1, SH2B3, SRSF2, TET2, and TP53), they detected CH in 17.6% of the patients. Not surprisingly, CH was associated with higher age at the blood draw and history of prior chemotherapy treatment. In addition, CH with PPM1D and TP53 mutations was almost exclusively identified in patients who received at least one line of platinum-based chemotherapy. This is consistent with the preclinical findings that platinum chemotherapy promotes positive selection of CH with DNA damage pathway mutations, PPM1D and TP53 (3, 4).