The early detection of tumors upon initial diagnosis or during routine surveillance is important for improving survival outcomes. Here, we investigated the feasibility and clinical significance of circulating tumor DNA (ctDNA) detection for Extranodal NK/T-cell lymphoma, nasal type (ENTKL). The plasma ctDNA assessment was based on blood specimens collected from 65 newly diagnosed patients with ENKTL in the hematology medical center of Xinqiao Hospital. Longitudinal samples collected under chemotherapy were also included. The gene mutation spectrum of ENKTL was analyzed via next generation sequencing. We found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%) and NOTCH1 (7.7%). The mutation allele frequencies of ATM and JAK3 were significantly correlated with the disease stage, and mutated KMT2D, ASXL3 and JAK3 were positively correlated with the metabolic tumor burden of the patients. Compared with the tumor tissue, ctDNA profiling showed good concordance (93.75%). Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequencies of the genes. Compared with PET/CT, ctDNA has more advantages in tracking residual disease in patients. In addition, patients with mutated KMT2D had higher expression compared with those with wild type, and mutated KMT2D predicted poor prognosis. Our results unveil the mutation spectrum of ENKTL patients’ plasma, which can be used to monitor the disease status of the patients exactly, and KMT2D is the most frequently mutated gene with prognosis prediction value. The application of ctDNA sequencing can provide precision treatment strategies for patients. This study is registered with chictr.org ( ChiCTR1800014813 , registered 7 February, 2018-Retrospectively registered).

中文翻译：

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血浆循环肿瘤 DNA 评估显示 KMT2D 是结外 NK/T 细胞淋巴瘤的潜在不良预后因素。

在初步诊断或常规监测期间及早发现肿瘤对于改善生存结果很重要。在这里，我们研究了循环肿瘤 DNA (ctDNA) 检测对结外 NK/T 细胞淋巴瘤、鼻型 (ENTKL) 的可行性和临床意义。血浆 ctDNA 评估基于新桥医院血液医学中心 65 例新诊断 ENKTL 患者的血液样本。还包括在化疗下收集的纵向样本。通过二代测序分析ENKTL的基因突变谱。我们发现突变频率最高的基因是 KMT2D (23.1%)、APC (12.3%)、ATM (10.8%)、ASXL3 (9.2%)、JAK3 (9.2%)、SETD2 (9.2%)、TP53 (9.2%)和 NOTCH1 (7.7%)。ATM和JAK3的突变等位基因频率与疾病分期显着相关，突变的KMT2D、ASXL3和JAK3与患者代谢性肿瘤负荷呈正相关。与肿瘤组织相比，ctDNA分析显示出良好的一致性（93.75%）。连续 ctDNA 分析表明，化疗可以减少基因的数量和突变等位基因频率。与PET/CT相比，ctDNA在追踪患者残留病灶方面更具优势。此外，与野生型相比，KMT2D突变患者的表达更高，并且突变的KMT2D预示着预后不良。我们的结果揭示了ENKTL患者血浆的突变谱，可用于准确监测患者的疾病状态，KMT2D是最常突变的基因，具有预后预测价值。ctDNA测序的应用可以为患者提供精准的治疗策略。本研究已在 chictr.org 注册（ChiCTR1800014813，2018 年 2 月 7 日注册-回顾性注册）。