Abstract
Extranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive hematological malignancy with poor prognosis. Early detection of tumors at initial diagnosis or during routine surveillance is important for improving survival outcomes. Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool for monitoring disease status. Here, we assessed the gene mutation spectrum of plasma ctDNA in ENKTL by cancer personalized profiling sequencing (CAPP-Seq). We found that the most frequently mutated genes were MGA (33.3%), TP53 (30%), ASXL3 (28.3%), DDX3X (25%), BCORL1 (25%), TRAF3 (21.7%), NOTCH3 (21.7%), STAT5B (21.7%), EP300 (21.7%), APC (20%), ATM (18.3%), TNFRSF14 (16.7%), KMT2D (16.7%), EZH2 (16.7%) and SETD2 (16.7%). The mutation frequencies of MGA and TP53 were significantly higher in stage III-IV, and mutations in MGA, TP53, and NOTCH3, et al were significantly correlated with the metabolic tumor burden of the patients. Compared with tumor tissue DNA, ctDNA profiling showed good concordance. Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequency of genes. Compared with PET/CT, ctDNA has more advantages for tracking residual disease in patients. In addition, we also found that mutated MGA, TP53, SETD2, and APC predicted poor prognosis in patients. Collectively, our results provide evidence that ctDNA may serve as a novel precision medicine biomarker in ENKTL.