Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas

• DOI: 10.4143/crt.2022.017
• Publication Date: 2022-03-02T00:55:50Z
• Authors: Seok Jin Kim; Yeon Jeong Kim; Sang Eun Yoon; Kyung Ju Ryu; Bon Park; Donghyun Park; Duck Cho; Hyun-Young Kim; Junhun Cho; Young Hyeh Ko; Woong-Yang Park; Won Seog Kim
• Keywords: 0301 basic medicine; 03 medical and health sciences; Genotype; Mutation; Biomarkers, Tumor; Humans; Lymphoma, T-Cell, Peripheral; Original Article; Neoplasm Recurrence, Local; Circulating Tumor DNA; 3. Good health

Purpose Plasma circulating tumor DNA (ctDNA) could reflect the genetic alterations present in tumor tissues. However, there is little information about the clinical relevance of cell-free DNA genotyping in peripheral T-cell lymphoma (PTCL).Materials and Methods After targeted sequencing plasma cell-free DNA of patients with various subtypes of PTCL (n=94), we analyzed the mutation profiles of plasma ctDNA samples and their predictive value of dynamic ctDNA monitoring for treatment outcomes.Results Plasma ctDNA mutations were detected in 53 patients (56%, 53/94), and the detection rate of somatic mutations was highest in angioimmunoblastic T-cell lymphoma (24/31, 77%) and PTCL, not otherwise specified (18/29, 62.1%). Somatic mutations were detected in 51 of 66 genes that were sequenced, including the following top 10 ranked genes: RHOA, CREBBP, KMT2D, TP53, IDH2, ALK, MEF2B, SOCS1, CARD11, and KRAS. In the longitudinal assessment of ctDNA mutation, the difference in ctDNA mutation volume after treatment showed a significant correlation with disease relapse or progression. Thus, a ≥ 1.5-log decrease in genome equivalent (GE) between baseline and the end of treatment showed a significant association with better survival outcomes than a < 1.5-log decrease in GE.Conclusion Our results suggest the clinical relevance of plasma ctDNA analysis in patients with PTCL. However, our findings should be validated by a subsequent study with a larger study population and using a broader gene panel.