Abstract
BackgroundThe 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).MethodsThe 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.ResultsWe 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.ConclusionOur 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.Trial registrationThis study is registered with chictr.org (ChiCTR1800014813, registered 7 February, 2018-Retrospectively registered).
Highlights
Extranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive extranodal lymphoma of NK-cell or T-cell lineage, which is highly aggressive and heterogeneous disease, with predominance in males [1,2,3,4]
One potential biomarker for detection is circulating cell-free DNA, which comes from dying cells that release DNA fragments into circulation, and in tumor patients, some of the cfDNA primarily originates from apoptosis and necrotic cancer cells, which carry tumor-specific alterations [11,12,13,14]. circulating tumor DNA (ctDNA) sequencing is a promising tool for the real-time monitoring of tumor progression, and its application has been explored in multiple solid tumors [15]. ctDNA can reflect the temporal evolution of tumors
According to the Ann Arbor staging criteria, 14 patients were identified as stage I, 20 patients were identified as stage II, 13 patients were identified as stage III, and 18 patients were identified as stage IV (Table 1). ctDNA was successfully extracted from all patients and healthy individuals
Summary
Extranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive extranodal lymphoma of NK-cell or T-cell lineage, which is highly aggressive and heterogeneous disease, with predominance in males [1,2,3,4]. Current treatment strategies (such as the combination of chemotherapy, radiotherapy, targeted therapy) can improve the complete remission of patients, but most will relapse and progress [5,6,7]. For these patients, standard monitoring methods, including computed tomography (CT) and serum protein markers analysis upon initial diagnosis and during routine surveillance, are pivotal for therapeutic response evaluation; these tests have limitations of low sensitivity and specificity or false positivity. We investigated the feasibility and clinical significance of circulating tumor DNA (ctDNA) detection for Extranodal NK/T-cell lymphoma, nasal type (ENTKL)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
