Circulating free DNA and its potential in the diagnostics and therapy of malignant lymphoma

Česká verzia

Authors: S. Hricko ¹; V.- Navrkalová ^{1 3}; A. Janíková ¹
Authors place of work: Interní hematologická a onkologická klinika LF MU a FN Brno ¹; Centrum molekulární medicíny, CEITEC MU – Středoevropský technologický institut, MU Brno ²; Ústav lékařské genetiky a genomiky, LF MU Brno ³
Published in the journal: Klin Onkol 2023; 37(4): 273-280
Category: Reviews

Summary

Background: Malignant lymphomas represent a highly heterogeneous group of tumors with varied clinical behavior – from indolent to very aggressive forms with survival in the order of months. From the very beginning, these diseases are considered systemic, often occurring in several anatomical locations simultaneously. However, diagnosis and exact classification are usually inferred from a biopsy of a single pathological lymph node or infiltrate, even though clinical experience shows that the biological behavior of lymphoma is not necessarily identical across anatomical locations. In an effort to address this issue as well as the problem of biopsy of not easily accessible compartments, circulating free DNA (cfDNA), which contains circulating tumor DNA (ctDNA) released from dead tumor cells, has been extensively studied in recent years. This DNA is easily accessible from liquid biopsies such as blood or other patient‘s bodily fluids.

Purpose: This article summarizes current scientific knowledge on cfDNA and ctDNA, particularly in the context of malignant lymphoma, and foreshadows its potential future uses.

Conclusion: Detection and analysis of cfDNA represents a new approach that can lead to future improvements in all phases of lymphoma treatment from diagnostics to minimal residual disease monitoring.

Keywords:

Circulating tumor DNA – malignant lymphoma – liquid biopsy – minimal residual disease – circulating free DNA – disease monitoring

Zdroje

1. Alizadeh AA, Eisen MB, Davis RE et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000; 403 (6769): 503–511. doi: 10.1038/35000501.
2. Hans CP, Weisenburger DD, Greiner TC et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004; 103 (1): 275–282. doi: 10.1182/blood-2003-05-1545.
3. Wright GW, Huang DW, Phelan JD et al. A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications. Cancer Cell 2020; 37 (4): 551–568.e14. doi: 10.1016/j.ccell.2020.03.015.
4. Sorigue M, Sancho J-M. Recent landmark studies in follicular lymphoma. Blood Rev 2019; 35: 68–80. doi: 10.1016/j.blre.2019.03.006.
5. Cheson BD, Nowakowski G, Salles G. Diffuse large B-cell lymphoma: new targets and novel therapies. Blood Cancer J 2021; 11 (4): 68. doi: 10.1038/s41408-021-00456-w.
6. McEwen AE, Leary SES, Lockwood CM. Beyond the blood: CSF-derived cfDNA for diagnosis and characterization of CNS tumors. Front Cell Dev Biol 2020; 8: 45. doi: 10.3389/fcell.2020.00045.
7. Bobillo S, Crespo M, Escudero L et al. Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas. Haematologica 2021; 106 (2): 513–521. doi: 10.3324/haematol.2019.241208.
8. Hummelink K, Muller M, Linders TC et al. Cell-free DNA in the supernatant of pleural effusion can be used to detect driver and resistance mutations, and can guide tyrosine kinase inhibitor treatment decisions. ERJ Open Res 2019; 5 (1): 00016–2019. doi: 10.1183/23120541.00016-2019.
9. Werner B, Yuwono N, Duggan J et al. Cell-free DNA is abundant in ascites and represents a liquid biopsy of ovarian cancer. Gynecol Oncol 2021; 162 (3): 720–727. doi: 10.1016/j.ygyno.2021.06.028.
10. Berry JL, Xu L, Murphree AL et al. Potential of aqueous humor as a surrogate tumor biopsy for retinoblastoma. JAMA Ophthalmol 2017; 135 (11): 1221–1230. doi: 10.1001/jamaophthalmol.2017.4097.
11. Berry JL, Xu L, Kooi I et al. Genomic cfDNA analysis of aqueous humor in retinoblastoma predicts eye salvage: the surrogate tumor biopsy for retinoblastoma. Mol Cancer Res 2018; 16 (11): 1701–1712. doi: 10.1158/1541-7786.MCR-18-0369.
12. Lone SN, Nisar S, Masoodi T et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments. Mol Cancer 2022; 21 (1): 79. doi: 10.1186/s12943-022-01543-7.
13. Delarue R, Haioun C, Ribrag V et al. CHOP and DHAP plus rituximab followed by autologous stem cell transplantation in mantle cell lymphoma: a phase 2 study from the Groupe d’Etude des Lymphomes de l’Adulte. Blood 2013; 121 (1): 48–53. doi: 10.1182/blood-2011-09-370320.
14. Wan Mohd Zohdi WA, Ismail AZ, Yusof N et al. Rare but potentially fatal presentations of diffuse large B-cell lymphoma: leukemic phase or hemophagocytic syndrome in bone marrow. Clin Pathol 2022; 15: 2632010X211070774. doi: 10.1177/2632010X211070774.
15. Moss J, Magenheim J, Neiman D et al. Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease. Nat Commun 2018; 9 (1): 5068. doi: 10.1038/s41467-018-07466-6.
16. Liu X, Ren J, Luo N et al. Comprehensive DNA methylation analysis of tissue of origin of plasma cell-free DNA by methylated CpG tandem amplification and sequencing (MCTA-Seq). Clin Epigenetics 2019; 11 (1): 93. doi: 10.1186/s13148-019-0689-y.
17. Snyder MW, Kircher M, Hill AJ et al. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell 2016; 164 (1–2): 57–68. doi: 10.1016/j.cell.2015.11.050.
18. Jahr S, Hentze H, Englisch S et al. DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 2001; 61 (4): 1659–1665.
19. Leon SA, Shapiro B, Sklaroff DM et al. Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 1977; 37 (3): 646–650.
20. McBride DJ, Orpana AK, Sotiriou C et al. Use of cancer-specific genomic rearrangements to quantify disease burden in plasma from patients with solid tumors. Genes Chromosomes Cancer 2010; 49 (11): 1062–1069. doi: 10.1002/gcc.20815.
21. Lo YMD, Chan LYS, Lo K-W et al. Quantitative analysis of cell-free Epstein-Barr virus DNA in plasma of patients with nasopharyngeal carcinoma. Cancer Res 1999; 59 (6): 1188–1191.
22. Chan KCA, Hung ECW, Woo JKS et al. Early detection of nasopharyngeal carcinoma by plasma Epstein-Barr virus DNA analysis in a surveillance program. Cancer 2013; 119 (10): 1838–1844. doi: 10.1002/cncr.28001.
23. Xian RR, Kinyera T, Otim I et al. Plasma EBV DNA: a promising diagnostic marker for endemic Burkitt lymphoma. Front Oncol 2021; 11: 804083. doi: 10.3389/fonc.2021.804083.
24. Lee K, Tripathi A. Parallel DNA extraction from whole blood for rapid sample generation in genetic epidemiological studies. Front Genet 2020; 11: 374. doi: 10.3389/fgene.2020.00374.
25. Gedvilaitė V, Schveigert D, Cicėnas S. Cell-free DNA in non-small cell lung cancer. Acta Medica Litu 2017; 24 (2): 138–144. doi: 10.6001/actamedica.v24i2.3495.
26. Lanman RB, Mortimer SA, Zill OA et al. Analytical and clinical validation of a digital sequencing panel for quantitative, highly accurate evaluation of cell-free circulating tumor DNA. PLoS One 2015; 10 (10): e0140712. doi: 10.1371/journal.pone.0140712.
27. Schwarzenbach H, Stoehlmacher J, Pantel K et al. Detection and monitoring of cell-free DNA in blood of patients with colorectal cancer. Ann N Y Acad Sci 2008; 1137: 190–196. doi: 10.1196/annals.1448.025.
28. Scherer F, Kurtz DM, Diehn M et al. High-throughput sequencing for noninvasive disease detection in hematologic malignancies. Blood 2017; 130 (4): 440–452. doi: 10.1182/blood-2017-03-735639.
29. Kang Q, Henry NL, Paoletti C et al. Comparative analysis of circulating tumor DNA stability In K3EDTA, Streck, and CellSave blood collection tubes. Clin Biochem 2016; 49 (18): 1354–1360. doi: 10.1016/j.clinbiochem.2016.03.012.
30. Alidousty C, Brandes D, Heydt C et al. Comparison of blood collection tubes from three different manufacturers for the collection of cell-free DNA for liquid biopsy mutation testing. J Mol Diagn 2017; 19 (5): 801–804. doi: 10.1016/j.jmoldx.2017.06.004.
31. Lee J-S, Kim M, Seong M-W et al. Plasma vs. serum in circulating tumor DNA measurement: characterization by DNA fragment sizing and digital droplet polymerase chain reaction. Clin Chem Lab Med 2020; 58 (4): 527–532. doi: 10.1515/cclm-2019-0896.
32. Chen Q, Zhang Z-H, Wang S et al. Circulating cell-free DNA or circulating tumor DNA in the management of ovarian and endometrial cancer. Onco Targets Ther 2019; 12: 11517–11530. doi: 10.2147/OTT.S227156.
33. Lauer EM, Mutter J, Scherer F. Circulating tumor DNA in B-cell lymphoma: technical advances, clinical applications, and perspectives for translational research. Leukemia 2022; 36 (9): 2151–2164. doi: 10.1038/s41375-022-01618-w.
34. Zhu G, Ye X, Dong Z et al. Highly sensitive droplet digital PCR method for detection of EGFR-activating mutations in plasma cell-free DNA from patients with advanced non-small cell lung cancer. J Mol Diagn 2015; 17 (3): 265–272. doi: 10.1016/j.jmoldx.2015.01.004.
35. Watanabe M, Kawaguchi T, Isa S et al. Ultra-sensitive detection of the pretreatment EGFR T790M mutation in non-small cell lung cancer patients with an EGFR-activating mutation using droplet digital PCR. Clin Cancer Res 2015; 21 (15): 3552–3560. doi: 10.1158/1078-0432.CCR-14-2151.
36. Sanmamed MF, Fernández-Landázuri S, Rodríguez C et al. Quantitative cell-free circulating BRAFV600E mutation analysis by use of droplet digital PCR in the follow-up of patients with melanoma being treated with BRAF inhibitors. Clin Chem 2015; 61 (1): 297–304. doi: 10.1373/clinchem.2014.230235.
37. Hattori K, Sakata-Yanagimoto M, Suehara Y et al. Clinical significance of disease-specific MYD88 mutations in circulating DNA in primary central nervous system lymphoma. Cancer Sci 2018; 109 (1): 225–230. doi: 10.1111/cas.13450.
38. Drandi D, Genuardi E, Dogliotti I et al. Highly sensitive MYD88L265P mutation detection by droplet digital polymerase chain reaction in Waldenström macroglobulinemia. Haematologica 2018; 103 (6): 1029–1037. doi: 10.3324/haematol.2017.186528.
39. Schmitz R, Wright GW, Huang DW et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med 2018; 378 (15): 1396–1407. doi: 10.1056/ NEJMoa1801445.
40. Kurtz DM, Green MR, Bratman SV et al. Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood 2015; 125 (24): 3679–3687. doi: 10.1182/blood-2015-03-635 169.
41. Newman AM, Bratman SV, To J et al. An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage. Nat Med 2014; 20 (5): 548–554. doi: 10.1038/nm.3519.
42. Kurtz DM, Soo J, Co Ting Keh L et al. Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nat Biotechnol 2021; 39 (12): 1537–1547. doi: 10.1038/s41587-021-00981-w.
43. Lam SN, Zhou YC, Chan YM et al. Comparison of target enrichment platforms for circulating tumor DNA detection. Sci Rep 2020; 10 (1): 4124. doi: 10.1038/s41598-020-60375-x.
44. Wu H-T, Kalashnikova E, Mehta S et al. Characterization of clonal hematopoiesis of indeterminate potential mutations from germline whole exome sequencing data. J Clin Oncol 2020; 38 (15 Suppl): 1525. doi: 10.1200/JCO.2020.38.15_suppl.1525.
45. Razavi P, Li BT, Brown DN et al. High-intensity sequencing reveals the sources of plasma circulating cell--free DNA variants. Nat Med 2019; 25 (12): 1928–1937. doi: 10.1038/s41591-019-0652-7.
46. Scherer F, Kurtz DM, Newman AM et al. Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA. Sci Transl Med 2016; 8 (364): 364ra155. doi: 10.1126/scitranslmed.aai8545.
47. Thandra KC, Barsouk A, Saginala K et al. Epidemiology of non-Hodgkin’s lymphoma. Med Sci 2021; 9 (1): 5. doi: 10.3390/medsci9010005.
48. Roschewski M, Rossi D, Kurtz DM et al. Circulating tumor DNA in lymphoma: principles and future directions. Blood Cancer Discov 2022; 3 (1): 5–15. doi: 10.1158/2643-3230.BCD-21-0029.
49. Vandenberghe P, Wlodarska I, Tousseyn T et al. Non-invasive detection of genomic imbalances in Hodgkin/Reed-Sternberg cells in early and advanced stage Hodgkin’s lymphoma by sequencing of circulating cell-free DNA: a technical proof-of-principle study. Lancet Haematol 2015; 2 (2): e55–65. doi: 10.1016/S2352-3026 (14) 00039-8.
50. Sarkozy C, Huet S, Carlton VEH et al. The prognostic value of clonal heterogeneity and quantitative assessment of plasma circulating clonal IG-VDJ sequences at diagnosis in patients with follicular lymphoma. Oncotarget 2017; 8 (5): 8765–8774. doi: 10.18632/oncotarget.14448.
51. Sakata-Yanagimoto M, Nakamoto-Matsubara R, Komori D et al. Detection of the circulating tumor DNAs in angioimmunoblastic T-cell lymphoma. Ann Hematol 2017; 96 (9): 1471–1475. doi: 10.1007/s00277-017-3038-2.
52. Kurtz DM, Scherer F, Jin MC et al. Circulating tumor DNA measurements as early outcome predictors in diffuse large B-cell lymphoma. J Clin Oncol 2018; 36 (28): 2845–2853. doi: 10.1200/JCO.2018.78.5246.
53. Tabari E, Lovejoy AF, Lin H et al. Molecular characteristics and disease Burden metrics determined by next-generation sequencing on circulating tumor DNA correlate with progression free survival in previously untreated diffuse large B-cell lymphoma. Blood 2019; 134 (Suppl 1): 490. doi: 10.1182/blood-2019-123633.
54. Alig S, Macaulay CW, Kurtz DM et al. Short diagnosis-to-treatment interval is associated with higher circulating tumor DNA levels in diffuse large B-cell lymphoma. J Clin Oncol 2021; 39 (23): 2605–2616. doi: 10.1200/JCO.20.02573.
55. Oki Y, Neelapu SS, Fanale M et al. Detection of classical Hodgkin lymphoma specific sequence in peripheral blood using a next-generation sequencing approach. Br J Haematol 2015; 169 (5): 689–693. doi: 10.1111/bjh.13349.
56. Camus V, Viennot M, Lequesne J et al. Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: a prospective study. Haematologica 2021; 106 (1): 154–162. doi: 10.3324/haematol.2019.237719.
57. De Mattos-Arruda L, Mayor R, Ng CKY et al. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma. Nat Commun 2015; 6: 8839. doi: 10.1038/ncomms9839.
58. Scherer F. Profiling of circulating tumor DNA for noninvasive disease detection, risk stratification, and MRD monitoring in patients with CNS lymphoma. ASH 2021.
59. Yoon SE, Kim YJ, Shim JH et al. Plasma circulating tumor DNA in patients with primary central nervous system lymphoma. Cancer Res Treat 2022; 54 (2): 597–612. doi: 10.4143/crt.2021.752.
60. Wang X, Su W, Gao Y et al. A pilot study of the use of dynamic cfDNA from aqueous humor and vitreous fluid for the diagnosis and treatment monitoring of vitreoretinal lymphomas. Haematologica 2022; 107 (9): 2154–2162. doi: 10.3324/haematol.2021.279908.
61. Jovanovski A, Petiti J, Giugliano E et al. Standardization of BCR-ABL1 p210 monitoring: from nested to digital PCR. Cancers 2020; 12 (11): 3287. doi: 10.3390/cancers12113287.
62. Janikova A, Mayer J, Kren L et al. The persistence of t (14; 18) -bearing cells in lymph nodes of patients with follicular lymphoma in complete remission: the evidence for „a lymphoma stem cell“. Leuk Lymphoma 2009; 50 (7): 1102–1109. doi: 10.1080/10428190902927 005.
63. Radford J, Illidge T, Counsell N et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. N Engl J Med 2015; 372 (17): 1598–1607. doi: 10.1056/NEJMoa1408648.
64. El-Galaly TC, Jakobsen LH, Hutchings M et al. Routine imaging for diffuse large B-cell lymphoma in first complete remission does not improve post-treatment survival: a Danish-Swedish population-based study. J Clin Oncol 2015; 33 (34): 3993–3998. doi: 10.1200/JCO.2015.62. 0229.
65. Macaulay C, Alig S, Kurtz DM et al. Interim circulating tumor DNA as a prognostic biomarker in the setting of interim PET-based adaptive therapy for DLBCL. Blood 2019; 134 (Suppl 1): 1600. doi: 10.1182/blood-2019-131278.
66. Roschewski M, Dunleavy K, Pittaluga S et al. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol 2015; 16 (5): 541–549. doi: 10.1016/S1470-2045 (15) 70106-3.
67. Lakhotia R, Melani C, Dunleavy K et al. Circulating tumor DNA predicts therapeutic outcome in mantle cell lymphoma. Blood Adv 2022; 6 (8): 2667–2680. doi: 10.1182/bloodadvances.2021006397.
68. Merryman RW, Redd RA, Taranto E et al. Prognostic value of circulating tumor DNA (ctDNA) in autologous stem cell graft and post-transplant plasma samples among patients with diffuse large B-cell lymphoma. Blood 2020; 136 (Suppl 1): 22–23. doi: 10.1182/blood-2020-140965.
69. Zorofchian S, Lu G, Zhu J-J et al. Detection of the MYD88 p.L265P mutation in the CSF of a patient with secondary central nervous system lymphoma. Front Oncol 2018; 8: 382. doi: 10.3389/fonc.2018.00382.
70. Goodman AM, Holden KA, Jeong A-R et al. Assessing CAR T-cell therapy response using genome-wide sequencing of cell-free DNA in patients with B-cell lymphomas. Transplant Cell Ther 2022; 28 (1): 30.e1–30.e7. doi: 10.1016/j.jtct.2021.10.007.
71. Mika T, Thomson J, Nilius-Eliliwi V et al. Quantification of cell-free DNA for the analysis of CD19-CAR-T cells during lymphoma treatment. Mol Ther Methods Clin Dev 2021; 23: 539–550. doi: 10.1016/j.omtm.2021.10.009.