본문 바로가기
KERD
논문KCI 등재

Circulating Tumor DNA Reflects Histologic and Clinical Characteristics of Various Lymphoma Subtypes

김홍경|김진주|김혜민|이승태|최종락|김수정|신새암|황도유
대한암학회 (Korean Cancer Association)|2024.01|Cancer Research and Treatment|제56권 제1호|pp. 314-323|DOI 10.4143/crt.2023.667

0

조회

0

다운로드

0

인용

0

참고문헌

키워드

LymphomaLiquid biopsyCirculating tumor DNA
주제분류의학일반

초록

Purpose We designed and evaluated the clinical performance of a plasma circulating tumor DNA (ctDNA) panel of 112 genes in various subtypes of lymphoma.Materials and Methods Targeted deep sequencing with an error-corrected algorithm was performed in ctDNA from plasma samples that were collected before treatment in 42 lymphoma patients. Blood buffy coat was utilized as a germline control. We evaluated the targeted gene panel using mutation detection concordance on the plasma samples with matched tissue samples analyzed the mutation profiles of the ctDNA.Results Next-generation sequencing analysis using matched tissue samples was available for 18 of the 42 patients. At least one mutation was detected in the majority of matched tissue biopsy samples (88.9%) and plasma samples (83.3%). A considerable number of mutations (40.4%) that were detected in the tissue samples were also found in the matched plasma samples. Majority of patients (21/42) were diffuse large B cell lymphoma patients. The overall detection rate of ctDNA in patients was 85.7% (36/42). The frequently mutated genes included <i>PIM1, TET2, BCL2, KMT2D, KLHL6, HIST1H1E</i>, and <i>IRF8</i>. A cutoff concentration (4,506 pg/mL) of ctDNA provided 88.9% sensitivity and 82.1% specificity to predict ctDNA mutation detection. The ctDNA concentration correlated with elevated lactate dehydrogenase level and the disease stage.Conclusion Our design panel can detect many actionable gene mutations, including those at low frequency. Therefore, liquid biopsy can be applied clinically in the evaluation of lymphoma patients, especially in aggressive lymphoma patients.

Abstract

Purpose We designed and evaluated the clinical performance of a plasma circulating tumor DNA (ctDNA) panel of 112 genes in various subtypes of lymphoma. Materials and Methods Targeted deep sequencing with an error-corrected algorithm was performed in ctDNA from plasma samples that were collected before treatment in 42 lymphoma patients. Blood buffy coat was utilized as a germline control. We evaluated the targeted gene panel using mutation detection concordance on the plasma samples with matched tissue samples analyzed the mutation profiles of the ctDNA. Results Next-generation sequencing analysis using matched tissue samples was available for 18 of the 42 patients. At least one mutation was detected in the majority of matched tissue biopsy samples (88.9%) and plasma samples (83.3%). A considerable number of mutations (40.4%) that were detected in the tissue samples were also found in the matched plasma samples. Majority of patients (21/42) were diffuse large B cell lymphoma patients. The overall detection rate of ctDNA in patients was 85.7% (36/42). The frequently mutated genes included PIM1, TET2, BCL2, KMT2D, KLHL6, HIST1H1E, and IRF8. A cutoff concentration (4,506 pg/mL) of ctDNA provided 88.9% sensitivity and 82.1% specificity to predict ctDNA mutation detection. The ctDNA concentration correlated with elevated lactate dehydrogenase level and the disease stage. Conclusion Our design panel can detect many actionable gene mutations, including those at low frequency. Therefore, liquid biopsy can be applied clinically in the evaluation of lymphoma patients, especially in aggressive lymphoma patients.

참고문헌 (33)

  1. Roschewski M, "Circulating tumor DNA in lymphoma : principles and future directions", Blood Cancer Discov, 3, pp.5~15 (2022)
  2. Wright GW, "A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications", Cancer Cell, 37, pp.551~568 (2020)
  3. Satou A, "An update on the pathol ogy and molecular features of Hodgkin lymphoma", Cancers(Basel), 14, pp.2647~ (2022)
  4. Jiang Y, "Deep sequencing reveals clonal evolution patterns and mu tation events associated with relapse in B-cell lymphomas", Genome Biol, 15, pp.432~ (2014)
  5. Araf S, "Genomic profiling reveals spatial intra-tumor heteroge neity in follicular lymphoma", Leukemia, 32, pp.1261~1265 (2018)
  6. Kridel R, "Histological transformation and progression in follicular lym phoma : a clonal evolution study", PLoS Med, 13, pp.e1002197~ (2016)
  7. Scherer F, "Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA", Sci Transl Med, 8, pp.364ra155~ (2016)
  8. Lakhotia R, "Circulating tumour DNA in B-cell lymphomas : current state and future prospects", Br J Haematol, 193, pp.867~881 (2021)
  9. Bohers E, "Non-invasive monitoring of diffuse large B-cell lymphoma by cell-free DNA high-throughput targeted sequencing : analysis of a prospective cohort", Blood Cancer J, 8, pp.74~ (2018)
  10. Rivas-Delgado A, "Mutational landscape and tumor burden assessed by cell-free DNA in diffuse large B-cell lym phoma in a population-based study", Clin Cancer Res, 27, pp.513~521 (2021)
  11. Rossi D, "Diffuse large B-cell lymphoma genotyping on the liquid biopsy", Blood, 129, pp.1947~1957 (2017)
  12. Lee KS, "Analyti cal and clinical validation of cell-free circulating tumor DNA assay for the estimation of tumor mutational burden", Clin Chem, 68, pp.1519~1528 (2022)
  13. Kim H, "Copy number analysis by base-level normalization : an intuitive vis ualization tool for evaluating copy number variations", Clin Genet, 103, pp.35~44 (2023)
  14. Lauer EM, "Circulating tumor DNA in B-cell lymphoma: technical advances, clinical applications, and perspectives for translational research", Leukemia, 36, pp.2151~2164 (2022)
  15. Arzuaga-Mendez J, "Cell-free DNA as a biomarker in diffuse large B-cell lymphoma : a systematic review", Crit Rev Oncol Hematol, 139, pp.7~15 (2019)
  16. Chae YK, "Concordance of genomic alterations by next-gener ation sequencing in tumor tissue versus circulating tumor DNA in breast cancer", Mol Cancer Ther, 16, pp.1412~1420 (2017)
  17. Wyatt AW, "Concordance of circulating tumor DNA and matched metastatic tissue biopsy in prostate cancer", J Natl Cancer Inst, 109, pp.djx118~ (2017)
  18. Bourbon E, "How to obtain a high quality ctDNA in lymphoma patients : preana lytical tips and tricks", Pharmaceuticals, 14, pp.617~ (2021)
  19. Lanman RB, "Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evalu ation of cell-free circulating tumor DNA", PLoS One, 10, pp.e0140712~ (2015)
  20. Paweletz CP, "Does testing error underlie liquid biopsy discordance?", JCO Precis Oncol, 3, pp.1~3 (2019)
  21. Fernandez-Miranda I, "Monitoring of circulating tumor DNA predicts response to treatment and early progression in follicular lymphoma : results of a prospective pilot study", Clin Cancer Res, 29, pp.209~220 (2023)
  22. Kurtz DM, "Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma", J Clin Oncol, 36, pp.2845~2853 (2018)
  23. Zhang S, "Tracking the evolution of untreated high-intermediate", high-risk dif fuse large B-cell lymphoma by circulating tumour DNA, 2022, pp.196, 617~628
  24. Camus V, "Targeted genotyping of circulating tumor DNA for clas sical Hodgkin lymphoma monitoring : a prospective study", Haematologica, 106, pp.154~162 (2021)
  25. Lee JH, "Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell lymphoma : a meta-analysis", Sci Rep, 7, pp.1785~ (2017)
  26. Zhang H, "PIM1genetic alterations associated with distinct molecular pro f iles, phenotypes and drug responses in diffuse large B-cell lymphoma", Clin Transl Med, 12, pp.e808~ (2022)
  27. Kuo HP, "The role of PIM1 in the ibrutinib-resistant ABC sub type of diffuse large B-cell lymphoma", Am J Cancer Res, 6, pp.2489~2501 (2016)
  28. Shafie A, "Investigating single amino acid substitutions in PIM1kinase : a structural genomics approach", PLoS One, 16, pp.e0258929~ (2021)
  29. Bellon M, "Targeting Pim kinases in hematological cancers : molecular and clinical review", Mol Cancer, 22, pp.18~ (2023)
  30. Schuetz JM, "BCL2 mutations in diffuse large B-cell lym phoma", Leukemia, 26, pp.1383~1390 (2012)
  31. Correia C, "BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lym phoma", Blood, 125, pp.658~667 (2015)
  32. Bolen CR, "Prognostic impact of somatic mutations in diffuse large B-cell lymphoma and relationship to cell-of-origin : data from the phase III GOYA study", Haematologica, 105, pp.2298~2307 (2020)
  33. Heward J, "KDM5 inhibition offers a novel therapeutic strategy for the treatment of KMT2D mutant lymphomas", Blood, 138, pp.370~381 (2021)

관련 논문AI추천

Feasibility of Circulating Tumor DNA Analysis in Patients with Follicular Lymphoma김석진, 김원석, 남대근, 신승호, 윤상은, 조준훈대한암학회 · Cancer Research and Treatment2024 · 제56권 제3호Plasma Circulating Tumor DNA in Patients with Primary Central Nervous System Lymphoma조덕, 고영혜, 김석진, 김연정, 김원석, 문영철, 박동현, 박웅양, 심준호, 윤상은, 이경은, 조준훈대한암학회 · Cancer Research and Treatment2022 · 제54권 제2호Circulating Tumor DNA–Based Genotyping and Monitoring for Predicting Disease Relapses of Patients with Peripheral T-Cell Lymphomas박본, 조덕, 고영혜, 김석진, 김연정, 김원석, 김현영, 박동현, 박웅양, 유경주, 윤상은, 조준훈대한암학회 · Cancer Research and Treatment2023 · 제55권 제1호Feasibility of Circulating Tumor DNA Detection in the Cerebrospinal Fluid of Patients With Central Nervous System Involvement in Large B-Cell LymphomaKim Jin Ju, Kim Seok Jin, Kim Won Seog, Lee Seung-Tae, Park Bon, Park Mi Ri, Ryu Kyung Ju, Shin Saeam, Yoon Sang Eun대한진단검사의학회 · Annals of Laboratory Medicine2025 · 제45권 제1호Clinical Implications of Circulating Tumor DNA in Multiple Myeloma and Its Precursor DiseasesChung Yeun-Jun, Jung Seung-Hyun, Kim Na Yung, Lee Jung Yeon, Lim Ji-Young, Min Chang-Ki, Park Sung-Soo, Yun Sujin대한진단검사의학회 · Annals of Laboratory Medicine2025 · 제45권 제3호Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers김시현, 차용준, 한세원대한암학회 · Cancer Research and Treatment2023 · 제55권 제2호

이 간행물의 다른 논문 (30건)

Intensity-Modulated Radiation Therapy for Uterine Cervical Cancer to Reduce Toxicity and Enhance Efficacy – an Option or a Must?: A Narrative Review이세원, 이성종, 김성환, 김애란, 이종훈pp. 1-17Longitudinal Changes in Smoking Behaviors and Cancer-Related Mortality Risk in Middle-aged Korean Women김선주, 박보영, 김소연, TRANTHIXUANMAIpp. 18-26Trends and Clinical Characteristics of Next-Generation Sequencing-Based Genetic Panel Tests: An Analysis of Korean Nationwide Claims Data박해용, 임현선, 김은경, 최윤라, 심효섭, 장미, 허자윤pp. 27-36A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial김규현, 이근욱, 안희경, 김진수, 이윤규, 안호정, 임선민, 안명주, 김범석, 김혜련, 이현우pp. 37-47Lazertinib versus Gefitinib as First-Line Treatment for EGFR-Mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset왕장영, 이윤규, 신상원, 최진혁, 이종석, 김진수, 심병용, 김주항, 민영주, 이기형, 이영주, 박건욱, 고윤호, 김동완, 최석영, 강진형, 조은경, 이경원, 전상훈, 이성숙, 이경희, 김상위, 안명주, 조병철pp. 48-60
원문 보기