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

• Published in: Cancer research and treatment Vol. 55; no. 1; pp. 291 - 303
• Main Authors: Kim, Seok Jin, Kim, Yeon Jeong, Yoon, Sang Eun, Ryu, Kyung Ju, Park, Bon, Park, Donghyun, Cho, Duck, Kim, Hyun-Young, Cho, Junhun, Ko, Young Hyeh, Park, Woong-Yang, Kim, Won Seog
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.01.2023; 대한암학회
• Subjects: Biomarkers, Tumor - genetics; Circulating Tumor DNA - genetics; Genotype; Humans; Lymphoma, T-Cell, Peripheral - genetics; Mutation; Neoplasm Recurrence, Local; Original; 의학일반; Liquid biopsy; Biomarker; Peripheral T-cell lymphoma; Circulating tumor DNA
• ISSN: 1598-2998; 2005-9256; 2005-9256
• DOI: 10.4143/crt.2022.017

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.