Plasma circulating tumor DNA assessment reveals KMT2D as a potential poor prognostic factor in extranodal NK/T-cell lymphoma

• Published in: Biomarker research Vol. 8; no. 1; p. 27
• Main Authors: Li, Qiong, Zhang, Wei, Li, Jiali, Xiong, Jingkang, Liu, Jia, Chen, Ting, Wen, Qin, Zeng, Yunjing, Gao, Li, Gao, Lei, Zhang, Cheng, Kong, Peiyan, Peng, Xiangui, Liu, Yao, Zhang, Xi, Rao, Jun
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.07.2020; BioMed Central; BMC
• Subjects: Adenomatous polyposis coli; Alleles; Biomarkers; Cancer; Chemotherapy; Circulating tumor DNA; Deoxyribonucleic acid; Development and progression; DNA; ENKTL; Gene frequency; Gene mutations; Genes; Genetic aspects; Genomes; Hematology; Lymphocytes T; Lymphoma; Medical centers; Medical imaging; Minimal residual disease; Mutation; Mutation allele frequency; Next-generation sequencing; Non-Hodgkin's lymphomas; Notch1 protein; p53 Protein; Patients; PET imaging; Plasma; Point mutation; Population genetics; Prognosis; Software; Statistical analysis; Surveillance; T-cell lymphoma; Tumor proteins; Tumors; California; Palo Alto California; Ann Arbor Michigan; United States > US; China; Minimal residual disease; ENKTL; Prognosis; Mutation allele frequency; Circulating tumor DNA
• ISSN: 2050-7771; 2050-7771
• DOI: 10.1186/s40364-020-00205-4

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 (23.1%), (12.3%), (10.8%), (9.2%), (9.2%), (9.2%), (9.2%) and (7.7%). The mutation allele frequencies of and were significantly correlated with the disease stage, and mutated 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 had higher expression compared with those with wild type, and mutated 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 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).