Mutations found in cell-free DNAs of patients with malignant lymphoma at remission can derive from clonal hematopoiesis
Mutations found in cell-free DNAs of patients with malignant lymphoma at remission can derive from clonal hematopoiesis
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DOI：
10.1111/cas.14176
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发表时间：
2019-09-12
期刊：
影响因子：
5.7
通讯作者：
Chiba, Shigeru
中科院分区：
文献类型：
--
作者：
Suehara, Yasuhito;Sakata-Yanagimoto, Mamiko;Chiba, Shigeru
用于检测循环肿瘤DNA的无细胞DNA（cfDNA）分析已经集中于监测恶性淋巴瘤。然而，不确定潜能的克隆造血（CHIP）相关突变也可以通过cfDNA分析检测。我们的目的是研究在B细胞淋巴瘤患者中检测到的cfDNA突变的起源。选择MYD 88/CD 79 B、DNMT 3A和TP 53作为感兴趣的基因，代表以下类别中的每一个：淋巴瘤驱动基因、CHIP相关基因和淋巴瘤和CHIP之间共有的基因。75例B细胞淋巴瘤患者被纳入这项回顾性研究。对完全代谢反应（CMR）时的血清cfDNA进行TP 53（N = 75）和DNMT 3A（N = 49）测序。在可获得肿瘤样本的弥漫性大B细胞淋巴瘤（DLBCL）患者（N = 29）中分析MYD 88 p.L265P和CD 79 B p.Y196C/H突变。在CMR处，在cfDNA中分别检测到TP 53和DNMT 3A中的两个和七个突变。在骨髓单个核细胞（BMMC）或PBMC中检测到这些突变。虽然在肿瘤中也检测到了四种DNMT 3A突变，但肿瘤中变异等位基因频率的中位数（
Cell-free DNA (cfDNA) analysis to detect circulating tumor DNA has been focused on monitoring malignant lymphomas. However, clonal hematopoiesis of indeterminate potential (CHIP)-associated mutations can also be detected by cfDNA analysis. Our aim is to investigate the origin of mutations detected in cfDNA among B-cell lymphoma patients. MYD88/CD79B, DNMT3A, and TP53 were chosen as genes of interest, representing each of the following categories: lymphoma driver genes, CHIP-related genes, and genes shared between lymphoma and CHIP. Seventy-five B-cell lymphoma patients were included in this retrospective study. Serum cfDNAs at time of complete metabolic response (CMR) were sequenced for TP53 (N = 75) and DNMT3A (N = 49). MYD88 p.L265P and CD79B p.Y196C/H mutations were analyzed in diffuse large B-cell lymphoma (DLBCL) patients whose tumor samples were available (N = 29). Two and seven mutations in TP53 and DNMT3A, respectively, were detected in cfDNA at CMR. These mutations were detected in either bone marrow mononuclear cells (BMMC) or PBMC. Although four DNMT3A mutations were also detected in tumors, median variant allele frequencies in the tumors (