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Cancer Research and Treatment > Accepted Articles
doi: https://doi.org/10.4143/crt.2023.869    [Accepted]
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon1 , Seung-Ho Shin2, Dae Keun Nam2, Junhun Cho3, Won Seog Kim1,4, Seok Jin Kim1,4
1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Geninus Inc., Seoul, Korea
3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
4Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence  Seok Jin Kim ,Tel: 82-2-3410-1766, Fax: 82-2-3410-1754, Email: kstwoh@skku.edu
Received: July 23, 2023;  Accepted: January 15, 2024.  Published online: January 16, 2024.
*Sang Eun Yoon and Seung-Ho Shin contributed equally to this work.
The feasibility of sequencing circulating tumor DNA (ctDNA) in plasma as a biomarker to predict early relapse or poor prognosis in patients with follicular lymphoma (FL) receiving systemic immunochemotherapy is not clear.
Materials and Methods
We sequenced DNA from cell-free plasma that was serially obtained from newly diagnosed FL patients undergoing systemic immunochemotherapy. The mutation profiles of ctDNA at the time of diagnosis and at response evaluation and relapse and/or progression were compared with clinical course and treatment outcomes.
Forty samples from patients receiving rituximab-containing immunochemotherapy were analyzed. Baseline sequencing detected mutations in all cases, with the major detected mutations being KMT2C (50%), CREBBP (45%), and KMT2D (45%). The concentration of ctDNA and tumor mutation burden showed a significant association with survival outcome. In particular, the presence of mutations in CREBBP and TP53 showed poor prognosis compared with patients without them. Longitudinal analysis of ctDNA using serially collected plasma samples showed an association between persistence or reappearance of ctDNA mutations and disease relapse or progression.
Analysis of ctDNA mutations in plasma at diagnosis might help predict outcome of disease, while analysis during follow-up may help to monitor disease status of patients with advanced FL. However, the feasibility of ctDNA measurement must be improved in order for it to become an appropriate and clinically relevant test in FL patients.
Key words: Follicular lymphoma, Circulating Tumor DNA, Mutations, Prognosis
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