Cancer Research and Treatment

Original Articles

Hematologic malignancy

Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas: 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; Cancer Res Treat. 2023;55(1):291-303. Published online March 2, 2022; DOI: https://doi.org/10.4143/crt.2022.017

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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.

Citations

Citations to this article as recorded by

Clinical use of circulating tumor DNA analysis in patients with lymphoma
Bettina Bisig, Karine Lefort, Sylvain Carras, Laurence de Leval
Human Pathology.2025; 156: 105679. CrossRef
Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application
Zongyao Huang, Yao Fu, Hong Yang, Yehan Zhou, Min Shi, Qingyun Li, Weiping Liu, Junheng Liang, Liuqing Zhu, Sheng Qin, Huangming Hong, Yang Liu
Molecular Cancer.2024;[Epub] CrossRef
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
Cancer Research and Treatment.2024; 56(3): 920. CrossRef
Minimal residual disease detection in lymphoma: methods, procedures and clinical significance
Sijun Zhang, Xiangyu Wang, Zhenzhen Yang, Mengjie Ding, Mingzhi Zhang, Ken H. Young, Xudong Zhang
Frontiers in Immunology.2024;[Epub] CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
A practical approach to the modern diagnosis and classification of T- and NK-cell lymphomas
Laurence de Leval, Philippe Gaulard, Ahmet Dogan
Blood.2024; 144(18): 1855. CrossRef
In-depth circulating tumor DNA sequencing for prognostication and monitoring in natural killer/T-cell lymphomas
Jin Ju Kim, Hyun-Young Kim, Zisun Choi, So yoon Hwang, Hansol Jeong, Jong Rak Choi, Sang Eun Yoon, Won Seog Kim, Sun-Hee Kim, Hee-Jin Kim, Sang-Yong Shin, Seung-Tae Lee, Seok Jin Kim
Frontiers in Oncology.2023;[Epub] CrossRef
Circulating tumor DNA in NK/T and peripheral T cell lymphoma
Yu-Jia Huo, Wei-Li Zhao
Seminars in Hematology.2023; 60(3): 173. CrossRef
A genetic profiling guideline to support diagnosis and clinical management of lymphomas
Margarita Sánchez-Beato, Miriam Méndez, María Guirado, Lucía Pedrosa, Silvia Sequero, Natalia Yanguas-Casás, Luis de la Cruz-Merino, Laura Gálvez, Marta Llanos, Juan Fernando García, Mariano Provencio
Clinical and Translational Oncology.2023; 26(5): 1043. CrossRef

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Plasma Circulating Tumor DNA in Patients with Primary Central Nervous System Lymphoma: Sang Eun Yoon, Yeon Jeong Kim, Joon Ho Shim, Donghyun Park, Junhun Cho, Young Hyeh Ko, Woong-Yang Park, Yeung-Chul Mun, Kyoung Eun Lee, Duck Cho, Won Seog Kim, Seok Jin Kim; Cancer Res Treat. 2022;54(2):597-612. Published online July 23, 2021; DOI: https://doi.org/10.4143/crt.2021.752

Abstract PDF Supplementary Material PubReader ePub

Purpose
Analysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL.
Materials and Methods
Targeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018.
Results
Targeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment.
Conclusion
The plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

Citations

Citations to this article as recorded by

Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell Lymphoma
Seok Jin Kim, Jin Ju Kim, Mi Ri Park, Bon Park, Kyung Ju Ryu, Sang Eun Yoon, Won Seog Kim, Saeam Shin, Seung-Tae Lee
Annals of Laboratory Medicine.2025; 45(1): 90. CrossRef
Circulating tumor DNA in lymphoma: technologies and applications
Lina Fu, Xuerong Zhou, Xiaoyu Zhang, Xuhua Li, Fan Zhang, Hongcang Gu, Xiaoxue Wang
Journal of Hematology & Oncology.2025;[Epub] CrossRef
Detection of circulating tumor DNA in plasma of patients with primary CNS lymphoma by digital droplet PCR
Yujie Zhong, Geok Wee Tan, Johanna Bult, Nick Veltmaat, Wouter Plattel, Joost Kluiver, Roelien Enting, Arjan Diepstra, Anke van den Berg, Marcel Nijland
BMC Cancer.2024;[Epub] CrossRef
Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma
Jin-Hua Liang, Yi-Fan Wu, Hao-Rui Shen, Yue Li, Jun-Heng Liang, Rui Gao, Wei Hua, Chun-Yu Shang, Kai-Xin Du, Tong-Yao Xing, Xin-Yu Zhang, Chen-Xuan Wang, Liu-Qing Zhu, Yang W. Shao, Jian-Yong Li, Jia-Zhu Wu, Hua Yin, Li Wang, Wei Xu
Leukemia.2024; 38(7): 1541. CrossRef
Liquid biopsy for improving diagnosis and monitoring of CNS lymphomas: A RANO review
Lakshmi Nayak, Chetan Bettegowda, Florian Scherer, Norbert Galldiks, Manmeet Ahluwalia, Alexander Baraniskin, Louisa von Baumgarten, Jacoline E C Bromberg, Andrés J M Ferreri, Christian Grommes, Khê Hoang-Xuan, Julia Kühn, James L Rubenstein, Roberta Rudà
Neuro-Oncology.2024; 26(6): 993. CrossRef
Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma
Sang Eun Yoon, Seung-Ho Shin, Dae Keun Nam, Junhun Cho, Won Seog Kim, Seok Jin Kim
Cancer Research and Treatment.2024; 56(3): 920. CrossRef
Clinical applications of circulating tumor DNA in hematological malignancies: From past to the future
Jun-Ying Li, Li-Ping Zuo, Jian Xu, Chun-Yan Sun
Blood Reviews.2024; 68: 101237. CrossRef
Circulating Tumor DNA Profiling for Detection, Risk Stratification, and Classification of Brain Lymphomas
Jurik A. Mutter, Stefan K. Alig, Mohammad S. Esfahani, Eliza M. Lauer, Jan Mitschke, David M. Kurtz, Julia Kühn, Sabine Bleul, Mari Olsen, Chih Long Liu, Michael C. Jin, Charles W. Macaulay, Nicolas Neidert, Timo Volk, Michel Eisenblaetter, Sebastian Raue
Journal of Clinical Oncology.2023; 41(9): 1684. CrossRef
Clinical applications of circulating tumor DNA in central nervous system lymphoma
Anna Katharina Foerster, Eliza M. Lauer, Florian Scherer
Seminars in Hematology.2023; 60(3): 150. CrossRef
Genetic Profiling of Cell-Free DNA in Liquid Biopsies: A Complementary Tool for the Diagnosis of B-Cell Lymphomas and the Surveillance of Measurable Residual Disease
Gloria Figaredo, Alejandro Martín-Muñoz, Santiago Barrio, Laura Parrilla, Yolanda Campos-Martín, María Poza, Laura Rufián, Patrocinio Algara, Marina De La Torre, Ana Jiménez Ubieto, Joaquín Martínez-López, Luis-Felipe Casado, Manuela Mollejo
Cancers.2023; 15(16): 4022. CrossRef
Asian variant intravascular large B-cell lymphoma with highly suspected central nervous system involvement: A case report
Yong-Pyo Lee, Seung-Myoung Son, Jihyun Kwon
World Journal of Clinical Cases.2023; 11(33): 8058. CrossRef
The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies
Rafael Colmenares, Noemí Álvarez, Santiago Barrio, Joaquín Martínez-López, Rosa Ayala
Cancers.2022; 14(5): 1310. CrossRef

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General

Targeted Liquid Biopsy Using Irradiation to Facilitate the Release of Cell-Free DNA from a Spatially Aimed Tumor Tissue: Jae Myoung Noh, Yeon Jeong Kim, Ho Yun Lee, Changhoon Choi, Won-Gyun Ahn, Taeseob Lee, Hongryull Pyo, Jee Hyun Park, Donghyun Park, Woong-Yang Park; Cancer Res Treat. 2022;54(1):40-53. Published online May 25, 2021; DOI: https://doi.org/10.4143/crt.2021.151

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the feasibility of using an anatomically localized, target-enriched liquid biopsy (TLB) in mouse models of lung cancer.
Materials and Methods
After irradiating xenograft mouse with human lung cancer cell lines, H1299 (NRAS proto-oncogene, GTPase [NRAS] Q61K) and HCC827 (epidermal growth factor receptor [EGFR] E746-750del), circulating (cell-free) tumor DNA (ctDNA) levels were monitored with quantitative polymerase chain reaction on human long interspersed nuclear element-1 and cell line-specific mutations. We checked dose-dependency at 6, 12, or 18 Gy to each tumor-bearing mouse leg using 6-MV photon beams. We also analyzed ctDNA of lung cancer patients by LiquidSCAN, a targeted deep sequencing to validated the clinical performances of TLB method.
Results
Irradiation could enhance the detection sensitivity of NRAS Q61K in the plasma sample of H1299-xenograft mouse to 4.5- fold. While cell-free DNA (cfDNA) level was not changed at 6 Gy, ctDNA level was increased upon irradiation. Using double-xenograft mouse with H1299 and HCC827, ctDNA polymerase chain reaction analysis with local irradiation in each region could specify mutation type matched to transplanted cell types, proposing an anatomically localized, TLB. Furthermore, when we performed targeted deep sequencing of cfDNA to monitor ctDNA level in 11 patients with lung cancer who underwent radiotherapy, the average ctDNA level was increased within a week after the start of radiotherapy.
Conclusion
TLB using irradiation could temporarily amplify ctDNA release in xenograft mouse and lung cancer patients, which enables us to develop theragnostic method for cancer patients with accurate ctDNA detection.

Citations

Citations to this article as recorded by

Establishment of xenografts and methods to evaluate tumor burden for the three most frequent subclasses of pediatric-type diffuse high grade gliomas
Leire Balaguer-Lluna, Nagore G. Olaciregui, Rosario Aschero, Claudia Resa-Pares, Sonia Paco, Maria Cuadrado-Vilanova, Victor Burgueño, Merce Baulenas-Farres, Carles Monterrubio, Alejandro Manzanares, Eva Rodríguez, Cinzia Lavarino, Jaume Mora, Angel M. Ca
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Tina Moser, Ellen Heitzer
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Treatment Response Biomarkers: Working Toward Personalized Radiotherapy for Lung Cancer
Ashley Horne, Ken Harada, Katherine D. Brown, Kevin Lee Min Chua, Fiona McDonald, Gareth Price, Paul Martin Putora, Dominic G. Rothwell, Corinne Faivre-Finn
Journal of Thoracic Oncology.2024; 19(8): 1164. CrossRef
Modulating cell-free DNA biology as the next frontier in liquid biopsies
Shervin Tabrizi, Carmen Martin-Alonso, Kan Xiong, Sangeeta N. Bhatia, Viktor A. Adalsteinsson, J. Christopher Love
Trends in Cell Biology.2024;[Epub] CrossRef
Basic Science with Preclinical Models to Investigate and Develop Liquid Biopsy: What Are the Available Data and Is It a Fruitful Approach?
Benedetta Cena, Emmanuel Melloul, Nicolas Demartines, Olivier Dormond, Ismail Labgaa
International Journal of Molecular Sciences.2022; 23(10): 5343. CrossRef
Analytical and Clinical Validation of Cell-Free Circulating Tumor DNA Assay for the Estimation of Tumor Mutational Burden
Kwang Seob Lee, Jieun Seo, Choong-Kun Lee, Saeam Shin, Zisun Choi, Seungki Min, Jun Hyuek Yang, Woo Sun Kwon, Woobin Yun, Mi Ri Park, Jong Rak Choi, Hyun Cheol Chung, Seung-Tae Lee, Sun Young Rha
Clinical Chemistry.2022; 68(12): 1519. CrossRef

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