{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:54:52Z","timestamp":1784289292133,"version":"3.55.0"},"reference-count":141,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004622","name":"Dutch Cancer Society (KWF Kankerbestrijding)","doi-asserted-by":"publisher","award":["11137"],"award-info":[{"award-number":["11137"]}],"id":[{"id":"10.13039\/501100004622","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Classical Hodgkin lymphoma (cHL) represents a B-cell lymphoproliferative disease characterized by clonal immunoglobulin gene rearrangements and recurrent genomic aberrations in the Hodgkin Reed\u2013Sternberg cells in a reactive inflammatory background. Several methods are available for the molecular analysis of cHL on both tissue and cell-free DNA isolated from blood, which can provide detailed information regarding the clonal composition and genetic alterations that drive lymphoma pathogenesis. Clonality testing involving the detection of immunoglobulin and T cell receptor gene rearrangements, together with mutation analysis, represent valuable tools for cHL diagnostics, especially for patients with an atypical histological or clinical presentation reminiscent of a reactive lesion or another lymphoma subtype. In addition, clonality assessment may establish the clonal relationship of composite or subsequent lymphoma presentations within one patient. During the last few decades, more insight has been obtained on the molecular mechanisms that drive cHL development, including recurrently affected signaling pathways (e.g., NF-\u03baB and JAK\/STAT) and immune evasion. We provide an overview of the different approaches to characterize the molecular composition of cHL, and the implementation of these next-generation sequencing-based techniques in research and diagnostic settings.<\/jats:p>","DOI":"10.3390\/cancers14133222","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T20:53:02Z","timestamp":1656622382000},"page":"3222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Novel Approaches in Molecular Characterization of Classical Hodgkin Lymphoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4289-2807","authenticated-orcid":false,"given":"Diede A. G.","family":"van Bladel","sequence":"first","affiliation":[{"name":"Radboud University Medical Center, Department of Pathology, 6525 GA Nijmegen, The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy B. C.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Department of Hematology, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"van den Brand","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Department of Pathology, 6525 GA Nijmegen, The Netherlands"},{"name":"Pathology-DNA, Rijnstate Hospital, 6815 AD Arnhem, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie I.","family":"Kroeze","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Department of Pathology, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J. T. A.","family":"Groenen","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Department of Pathology, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Han J. M.","family":"van Krieken","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Department of Pathology, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konnie M.","family":"Hebeda","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Department of Pathology, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8029-9230","authenticated-orcid":false,"given":"Blanca","family":"Scheijen","sequence":"additional","affiliation":[{"name":"Radboud University Medical Center, Department of Pathology, 6525 GA Nijmegen, The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1158\/1055-9965.EPI-15-0281","article-title":"Time Trends in Rates of Hodgkin Lymphoma Histologic Subtypes: True Incidence Changes or Evolving Diagnostic Practice?","volume":"24","author":"Glaser","year":"2015","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_2","unstructured":"Swerdlow, S.H., Campo, E., Harris, N.L., and Pileri, S.A. (2017). Myeloproliferative neoplasms, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/path.2711","article-title":"The classical Hodgkin\u2019s lymphoma microenvironment and its role in promoting tumour growth and immune escape","volume":"221","author":"Aldinucci","year":"2010","journal-title":"J. Pathol."},{"key":"ref_4","unstructured":"Campo, E., Harris, N.L., Pileri, S.A., Jaffe, E.S., Stein, H., and Thiele, J. (2017). Mature B-cell neoplasms, WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1172\/JCI61245","article-title":"Hodgkin lymphoma","volume":"122","author":"Kuppers","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Parente, P., Zanelli, M., Sanguedolce, F., Mastracci, L., and Graziano, P. (2020). Hodgkin Reed-Sternberg-Like Cells in Non-Hodgkin Lymphoma. Diagnostics, 10.","DOI":"10.3390\/diagnostics10121019"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1097\/PAS.0000000000000561","article-title":"High-grade Transformation of Low-grade B-cell Lymphoma: Pathology and Molecular Pathogenesis","volume":"40","author":"Agbay","year":"2016","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1200\/JCO.2010.32.7577","article-title":"Transformation of indolent B-cell lymphomas","volume":"29","author":"Montoto","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s11899-014-0220-7","article-title":"Relapsed Hodgkin lymphoma: Management strategies","volume":"9","author":"Montanari","year":"2014","journal-title":"Curr. Hematol. Malig. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3322\/caac.21438","article-title":"Hodgkin lymphoma: A review and update on recent progress","volume":"68","author":"Shanbhag","year":"2018","journal-title":"CA Cancer J. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Brune, M.M., Juskevicius, D., Haslbauer, J., Dirnhofer, S., and Tzankov, A. (2021). Genomic Landscape of Hodgkin Lymphoma. Cancers, 13.","DOI":"10.3390\/cancers13040682"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Cuceu, C., Hempel, W.M., Sabatier, L., Bosq, J., Carde, P., and M\u2019Kacher, R. (2018). Chromosomal Instability in Hodgkin Lymphoma: An In-Depth Review and Perspectives. Cancers, 10.","DOI":"10.3390\/cancers10040091"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41375-021-01204-6","article-title":"Molecular biology of Hodgkin lymphoma","volume":"35","author":"Weniger","year":"2021","journal-title":"Leukemia"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Camus, V., and Jardin, F. (2021). Cell-Free DNA for the Management of Classical Hodgkin Lymphoma. Pharmaceuticals, 14.","DOI":"10.3390\/ph14030207"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1056\/NEJM199911113412007","article-title":"Cellular origin of human B-cell lymphomas","volume":"341","author":"Kuppers","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0952-7915(95)80010-7","article-title":"Somatic hypermutation","volume":"7","author":"Neuberger","year":"1995","journal-title":"Curr. Opin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1182\/blood.V95.4.1443.004k55_1443_1450","article-title":"Hodgkin and reed-sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription","volume":"95","author":"Marafioti","year":"2000","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.1073\/pnas.91.23.10962","article-title":"Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development","volume":"91","author":"Kuppers","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1182\/blood.V70.1.186.186","article-title":"Clonal immunoglobulin gene rearrangements in tissues involved by Hodgkin\u2019s disease","volume":"70","author":"Brinker","year":"1987","journal-title":"Blood"},{"key":"ref_20","first-page":"177","article-title":"Immunoglobulin and T cell receptor gene rearrangements in lymphoproliferative disorders","volume":"57","author":"Daus","year":"1989","journal-title":"Exp. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/ijc.2910400205","article-title":"Clonal rearrangements of T-cell receptor and immunoglobulin genes and immunophenotypic antigen expression in different subclasses of Hodgkin\u2019s disease","volume":"40","author":"Griesser","year":"1987","journal-title":"Int. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0145-2126(89)90134-3","article-title":"Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin\u2019s disease and Ki-1-positive anaplastic large cell lymphoma: Dissociation between phenotype and genotype","volume":"13","author":"Herbst","year":"1989","journal-title":"Leuk. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7942","DOI":"10.1073\/pnas.83.20.7942","article-title":"Immunoglobulin and T-cell receptor beta-chain gene rearrangement analysis of Hodgkin\u2019s disease: Implications for lineage determination and differential diagnosis","volume":"83","author":"Knowles","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","first-page":"3591","article-title":"Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin\u2019s disease","volume":"48","author":"Raghavachar","year":"1988","journal-title":"Cancer Res."},{"key":"ref_25","first-page":"331","article-title":"Rearrangement of immunoglobulin and T-cell receptor genes in Hodgkin\u2019s disease","volume":"131","author":"Roth","year":"1988","journal-title":"Am. J. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1182\/blood.V70.1.96.96","article-title":"Rearranged antigen receptor genes in Hodgkin\u2019s disease","volume":"70","author":"Sundeen","year":"1987","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1093\/ajcp\/104.4.419","article-title":"Clonal VDJ recombination of the immunoglobulin heavy chain gene by PCR in classical Hodgkin\u2019s disease","volume":"104","author":"Kamel","year":"1995","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/j.1365-2559.1995.tb00286.x","article-title":"Evaluation of clonal immunoglobulin heavy chain rearrangements in Hodgkin\u2019s disease using the polymerase chain reaction (PCR)","volume":"27","author":"Manzanal","year":"1995","journal-title":"Histopathology"},{"key":"ref_29","first-page":"679","article-title":"Molecular analysis of the IgH gene in 212 cases of Hodgkin\u2019s disease: Correlation of IgH clonality with the histologic and the immunocytochemical features","volume":"10","author":"Manzanal","year":"1997","journal-title":"Mod. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1038\/sj.leu.2403202","article-title":"Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936","volume":"17","author":"Langerak","year":"2003","journal-title":"Leukemia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1309\/AJCPK6SBE0XOODHB","article-title":"PCR assays detect B-lymphocyte clonality in formalin-fixed, paraffin-embedded specimens of classical hodgkin lymphoma without microdissection","volume":"134","author":"Burack","year":"2010","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1097\/PDM.0b013e318150d695","article-title":"Detection of immunoglobulin heavy chain gene rearrangements in classic hodgkin lymphoma using commercially available BIOMED-2 primers","volume":"17","author":"Chute","year":"2008","journal-title":"Diagn. Mol. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"951","DOI":"10.7754\/Clin.Lab.2015.141139","article-title":"Molecular Analysis of IGH and Incomplete IGH D-J Clonality Gene Rearrangements in Hodgkin Lymphoma Malignancies","volume":"61","author":"Ghorbian","year":"2015","journal-title":"Clin. Lab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1179\/1607845415Y.0000000035","article-title":"Evaluation of IGK and IGL molecular gene rearrangements according to the BIOMED-2 protocols for clinical diagnosis of Hodgkin lymphoma","volume":"21","author":"Ghorbian","year":"2016","journal-title":"Hematology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1111\/pin.12660","article-title":"Improved clonality detection in Hodgkin lymphoma using a semi-nested modification of the BIOMED-2 PCR assay for IGH and IGK rearrangements: A paraffin-embedded tissue study","volume":"68","author":"Han","year":"2018","journal-title":"Pathol. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.prp.2013.05.004","article-title":"Clonality testing of malignant lymphomas with the BIOMED-2 primers in a large cohort of 1969 primary and consultant biopsies","volume":"209","author":"Hartmann","year":"2013","journal-title":"Pathol. Res. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1007\/s12308-009-0024-1","article-title":"PCR clonality detection in Hodgkin lymphoma","volume":"2","author":"Hebeda","year":"2009","journal-title":"J. Hematop."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/sj.leu.2404049","article-title":"Validation of immunoglobulin gene rearrangement detection by PCR using commercially available BIOMED-2 primers","volume":"20","author":"McClure","year":"2006","journal-title":"Leukemia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1111\/j.1365-2559.2011.04135.x","article-title":"Improved clonality detection in Hodgkin lymphoma using the BIOMED-2-based heavy and kappa chain assay: A paraffin-embedded tissue study","volume":"60","author":"Tapia","year":"2012","journal-title":"Histopathology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/sj.leu.2404479","article-title":"Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936","volume":"21","author":"Evans","year":"2007","journal-title":"Leukemia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12308-011-0132-6","article-title":"The added value of immunoglobulin Kappa light chain gene (IGK) rearrangement analysis in suspected B-cell lymphomas: Three illustrative cases","volume":"5","author":"Gameiro","year":"2012","journal-title":"J. Hematop."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.5858\/2006-130-1772-GRACGH","article-title":"Gene rearrangement and comparative genomic hybridization studies of classic Hodgkin lymphoma expressing T-cell antigens","volume":"130","author":"Aguilera","year":"2006","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1136\/mp.52.1.37","article-title":"Hodgkin\u2019s disease: Immunoglobulin heavy and light chain gene rearrangements revealed in single Hodgkin\/Reed-Sternberg cells","volume":"52","author":"Deng","year":"1999","journal-title":"Mol. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1056\/NEJM199510053331403","article-title":"Hodgkin\u2019s disease with monoclonal and polyclonal populations of Reed-Sternberg cells","volume":"333","author":"Hummel","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/ajcp\/110.5.599","article-title":"Monoclonal IgH gene rearrangement in microdissected nodules from nodular sclerosis Hodgkin disease","volume":"110","author":"Izban","year":"1998","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/ijc.2910570607","article-title":"Detection of immunoglobulin heavy-chain gene rearrangement at the single-cell level in malignant lymphomas: No rearrangement is found in Hodgkin and Reed-Sternberg cells","volume":"57","author":"Roth","year":"1994","journal-title":"Int. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1182\/blood.V95.10.3020","article-title":"Detection of clonal T-cell receptor gamma-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease","volume":"95","author":"Seitz","year":"2000","journal-title":"Blood"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1084\/jem.184.4.1495","article-title":"Hodgkin and Reed-Sternberg cells in Hodgkin\u2019s disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells","volume":"184","author":"Kanzler","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_49","first-page":"1644","article-title":"Typing the histogenetic origin of the tumor cells of lymphocyte-rich classical Hodgkin\u2019s lymphoma in relation to tumor cells of classical and lymphocyte-predominance Hodgkin\u2019s lymphoma","volume":"63","author":"Brauninger","year":"2003","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1111\/bjh.13349","article-title":"Detection of classical Hodgkin lymphoma specific sequence in peripheral blood using a next-generation sequencing approach","volume":"169","author":"Oki","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1038\/s41379-021-00983-8","article-title":"Clonality assessment and detection of clonal diversity in classic Hodgkin lymphoma by next-generation sequencing of immunoglobulin gene rearrangements","volume":"35","author":"Rijntjes","year":"2022","journal-title":"Mod. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41375-019-0541-6","article-title":"Genotyping circulating tumor DNA of pediatric Hodgkin lymphoma","volume":"34","author":"Desch","year":"2020","journal-title":"Leukemia"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1084\/jem.191.2.387","article-title":"Rare occurrence of classical Hodgkin\u2019s disease as a T cell lymphoma","volume":"191","author":"Muschen","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1182\/blood-2012-06-439455","article-title":"Aberrant T-cell antigen expression in classical Hodgkin lymphoma is associated with decreased event-free survival and overall survival","volume":"121","author":"Venkataraman","year":"2013","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1038\/s41375-019-0496-7","article-title":"Standardized next-generation sequencing of immunoglobulin and T-cell receptor gene recombinations for MRD marker identification in acute lymphoblastic leukaemia; a EuroClonality-NGS validation study","volume":"33","author":"Bruggemann","year":"2019","journal-title":"Leukemia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1038\/s41375-019-0508-7","article-title":"Next-generation sequencing of immunoglobulin gene rearrangements for clonality assessment: A technical feasibility study by EuroClonality-NGS","volume":"33","author":"Scheijen","year":"2019","journal-title":"Leukemia"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.3109\/10428194.2010.486094","article-title":"Rare presentation of classical Hodgkin lymphoma with a clonal T-cell receptor gene rearrangement in the tissue","volume":"51","author":"Nguyen","year":"2010","journal-title":"Leuk. Lymphoma"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1097\/01.LAB.0000027839.98023.5A","article-title":"T-cell variant of classical Hodgkin\u2019s lymphoma with nodal and cutaneous manifestations demonstrated by single-cell polymerase chain reaction","volume":"82","author":"Willenbrock","year":"2002","journal-title":"Lab. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/ajcp\/aqab090","article-title":"How I Diagnose Angioimmunoblastic T-Cell Lymphoma","volume":"156","author":"Xie","year":"2021","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1097\/PAS.0b013e318268d9ff","article-title":"Follicular peripheral T-cell lymphoma expands the spectrum of classical Hodgkin lymphoma mimics","volume":"36","author":"Moroch","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5268","DOI":"10.1158\/1078-0432.CCR-10-1271","article-title":"Clonal relationship of classical hodgkin lymphoma and its recurrences","volume":"17","author":"Obermann","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/nrc.2017.7","article-title":"Liquid biopsies come of age: Towards implementation of circulating tumour DNA","volume":"17","author":"Wan","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/bjh.17719","article-title":"Liquid biopsy: A non-invasive approach for Hodgkin lymphoma genotyping","volume":"195","author":"Alcoceba","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1080\/10428194.2018.1492123","article-title":"Somatic mutations of cell-free circulating DNA detected by targeted next-generation sequencing and digital droplet PCR in classical Hodgkin lymphoma","volume":"60","author":"Bessi","year":"2019","journal-title":"Leuk. Lymphoma"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.3324\/haematol.2016.145102","article-title":"Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma","volume":"101","author":"Camus","year":"2016","journal-title":"Haematologica"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"154","DOI":"10.3324\/haematol.2019.237719","article-title":"Targeted genotyping of circulating tumor DNA for classical Hodgkin lymphoma monitoring: A prospective study","volume":"106","author":"Camus","year":"2021","journal-title":"Haematologica"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1182\/blood-2017-11-812073","article-title":"Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma","volume":"131","author":"Spina","year":"2018","journal-title":"Blood"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.jmoldx.2016.06.010","article-title":"Reliable Next-Generation Sequencing of Formalin-Fixed, Paraffin-Embedded Tissue Using Single Molecule Tags","volume":"18","author":"Eijkelenboom","year":"2016","journal-title":"J. Mol. Diagn."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Kou, R., Lam, H., Duan, H., Ye, L., Jongkam, N., Chen, W., Zhang, S., and Li, S. (2016). Benefits and Challenges with Applying Unique Molecular Identifiers in Next Generation Sequencing to Detect Low Frequency Mutations. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146638"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lin, C., Liu, X., Zheng, B., Ke, R., and Tzeng, C.M. (2021). Liquid Biopsy, ctDNA Diagnosis through NGS. Life, 11.","DOI":"10.3390\/life11090890"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/clinchem\/48.3.421","article-title":"Predominant hematopoietic origin of cell-free DNA in plasma and serum after sex-mismatched bone marrow transplantation","volume":"48","author":"Lui","year":"2002","journal-title":"Clin. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Chan, H.T., Chin, Y.M., Nakamura, Y., and Low, S.K. (2020). Clonal Hematopoiesis in Liquid Biopsy: From Biological Noise to Valuable Clinical Implications. Cancers, 12.","DOI":"10.3390\/cancers12082277"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","article-title":"Age-related clonal hematopoiesis associated with adverse outcomes","volume":"371","author":"Jaiswal","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1182\/blood-2017-04-777029","article-title":"DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions","volume":"130","author":"Buscarlet","year":"2017","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1056\/NEJMoa1409405","article-title":"Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence","volume":"371","author":"Genovese","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1038\/nm.3733","article-title":"Age-related mutations associated with clonal hematopoietic expansion and malignancies","volume":"20","author":"Xie","year":"2014","journal-title":"Nat. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1158\/2643-3230.BCD-20-0203","article-title":"Dissecting Clonal Hematopoiesis in Tissues of Classical Hodgkin Lymphoma Patients","volume":"2","author":"Venanzi","year":"2021","journal-title":"Blood Cancer Discov."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e55","DOI":"10.1016\/S2352-3026(14)00039-8","article-title":"Non-invasive detection of genomic imbalances in Hodgkin\/Reed-Sternberg cells in early and advanced stage Hodgkin\u2019s lymphoma by sequencing of circulating cell-free DNA: A technical proof-of-principle study","volume":"2","author":"Vandenberghe","year":"2015","journal-title":"Lancet Haematol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1634\/theoncologist.2018-0058","article-title":"Comprehensive Genomic Profiling of Hodgkin Lymphoma Reveals Recurrently Mutated Genes and Increased Mutation Burden","volume":"24","author":"Liang","year":"2019","journal-title":"Oncologist"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"485","DOI":"10.5858\/arpa.2020-0457-OA","article-title":"Assessment of Clonotypic Rearrangements and Minimal Residual Disease in Lymphoid Malignancies: A Large Cancer Center Experience Using clonoSEQ","volume":"146","author":"Hussaini","year":"2021","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1080\/14737159.2019.1627877","article-title":"ClonoSEQ assay for the detection of lymphoid malignancies","volume":"19","author":"Monter","year":"2019","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_82","first-page":"1171","article-title":"In-depth cell-free DNA sequencing reveals genomic landscape of Hodgkin\u2019s lymphoma and facilitates ultrasensitive residual disease detection","volume":"2","author":"Sobesky","year":"2021","journal-title":"Med (N. Y.)"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"323","DOI":"10.7150\/jca.6226","article-title":"Plasma cell-free DNA in paediatric lymphomas","volume":"4","author":"Mussolin","year":"2013","journal-title":"J. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"364","DOI":"10.7150\/jca.13593","article-title":"Kinetics of Circulating Plasma Cell-Free DNA in Paediatric Classical Hodgkin Lymphoma","volume":"7","author":"Primerano","year":"2016","journal-title":"J. Cancer"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"102731","DOI":"10.1016\/j.ebiom.2020.102731","article-title":"Circulating tumor DNA predicts response in Chinese patients with relapsed or refractory classical hodgkin lymphoma treated with sintilimab","volume":"54","author":"Shi","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5173","DOI":"10.1182\/blood-2012-07-444042","article-title":"Deep-sequencing approach for minimal residual disease detection in acute lymphoblastic leukemia","volume":"120","author":"Faham","year":"2012","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nm.3519","article-title":"An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage","volume":"20","author":"Newman","year":"2014","journal-title":"Nat. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3324\/haematol.2020.265165","article-title":"Bringing circulating tumor DNA to the clinic in Hodgkin lymphoma","volume":"106","author":"Kurtz","year":"2021","journal-title":"Haematologica"},{"key":"ref_89","first-page":"3188","article-title":"Validation of the EuroClonality-NGS DNA capture panel as an integrated genomic tool for lymphoproliferative disorders","volume":"5","author":"Stewart","year":"2021","journal-title":"Blood Adv."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1182\/blood.2019000568","article-title":"An etiological role for the Epstein-Barr virus in the pathogenesis of classical Hodgkin lymphoma","volume":"134","author":"Murray","year":"2019","journal-title":"Blood"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1182\/blood-2014-11-610436","article-title":"Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells","volume":"125","author":"Reichel","year":"2015","journal-title":"Blood"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1182\/blood-2017-11-814913","article-title":"Pervasive mutations of JAK-STAT pathway genes in classical Hodgkin lymphoma","volume":"131","author":"Tiacci","year":"2018","journal-title":"Blood"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4065","DOI":"10.1182\/bloodadvances.2019001012","article-title":"Genomic analyses of flow-sorted Hodgkin Reed-Sternberg cells reveal complementary mechanisms of immune evasion","volume":"3","author":"Wienand","year":"2019","journal-title":"Blood Adv."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1182\/blood.V77.6.1298.1298","article-title":"Cytogenetic studies in untreated Hodgkin\u2019s disease","volume":"77","author":"Tilly","year":"1991","journal-title":"Blood"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.3324\/haematol.12875","article-title":"Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin\u2019s lymphoma by array-based comparative genomic hybridization","volume":"93","author":"Hartmann","year":"2008","journal-title":"Haematologica"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/annonc\/13.S1.19","article-title":"Genetic instability in Hodgkin\u2019s lymphoma","volume":"13","author":"Re","year":"2002","journal-title":"Ann. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"10332","DOI":"10.1158\/0008-5472.CAN-06-1992","article-title":"Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma","volume":"66","author":"Klapper","year":"2006","journal-title":"Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/gcc.10266","article-title":"Classical Hodgkin lymphoma is associated with frequent gains of 17q","volume":"38","author":"Chui","year":"2003","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1182\/blood.V99.4.1381","article-title":"Classical Hodgkin lymphoma is characterized by recurrent copy number gains of the short arm of chromosome 2","volume":"99","author":"Joos","year":"2002","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1182\/blood-2009-12-257345","article-title":"Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome","volume":"116","author":"Steidl","year":"2010","journal-title":"Blood"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2690","DOI":"10.1200\/JCO.2016.66.4482","article-title":"PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome","volume":"34","author":"Roemer","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1182\/bloodadvances.2020003039","article-title":"The landscape of copy number variations in classical Hodgkin lymphoma: A joint KU Leuven and LYSA study on cell-free DNA","volume":"5","author":"Buedts","year":"2021","journal-title":"Blood Adv."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1182\/blood-2015-07-659938","article-title":"GNA13 loss in germinal center B cells leads to impaired apoptosis and promotes lymphoma in vivo","volume":"127","author":"Healy","year":"2016","journal-title":"Blood"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1038\/onc.2015.442","article-title":"Inactivating mutations in GNA13 and RHOA in Burkitt\u2019s lymphoma and diffuse large B-cell lymphoma: A tumor suppressor function for the G\u03b113\/RhoA axis in B cells","volume":"35","author":"Inoue","year":"2016","journal-title":"Oncogene"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41419-020-03311-1","article-title":"GNA13 regulates BCL2 expression and the sensitivity of GCB-DLBCL cells to BCL2 inhibitors in a palmitoylation-dependent manner","volume":"12","author":"Xia","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41591-018-0012-z","article-title":"ARID1A deficiency promotes mutability and potentiates therapeutic antitumor immunity unleashed by immune checkpoint blockade","volume":"24","author":"Shen","year":"2018","journal-title":"Nat. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/ijc.1438","article-title":"TP53 gene mutations in Hodgkin lymphoma are infrequent and not associated with absence of Epstein-Barr virus","volume":"94","author":"Maggio","year":"2001","journal-title":"Int. J. Cancer"},{"key":"ref_108","first-page":"519","article-title":"p53 mutations in Hodgkin\u2019s disease","volume":"75","author":"Chen","year":"1996","journal-title":"Lab. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41408-019-0195-7","article-title":"Genomic analyses of microdissected Hodgkin and Reed-Sternberg cells: Mutations in epigenetic regulators and p53 are frequent in refractory classic Hodgkin lymphoma","volume":"9","author":"Mata","year":"2019","journal-title":"Blood Cancer J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/ajcp\/106.6.728","article-title":"P53 expression in Reed-Sternberg cells does not correlate with gene mutations in Hodgkin\u2019s disease","volume":"106","author":"Medeiros","year":"1996","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.semcancer.2013.07.002","article-title":"The microenvironment in classical Hodgkin lymphoma: An actively shaped and essential tumor component","volume":"24","author":"Liu","year":"2014","journal-title":"Semin. Cancer Biol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"20160271","DOI":"10.1098\/rstb.2016.0271","article-title":"Epstein-Barr virus-associated lymphomas","volume":"372","author":"Rickinson","year":"2017","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"30","DOI":"10.21037\/aol-21-8","article-title":"The contribution of ebv to the pathogenesis of classical hodgkin lymphoma","volume":"5","author":"Vrzalikova","year":"2021","journal-title":"Ann. Lymphoma"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00430-018-0570-1","article-title":"Molecular mechanisms of EBV-driven cell cycle progression and oncogenesis","volume":"208","author":"Yin","year":"2019","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"9556","DOI":"10.1128\/JVI.76.18.9556-9561.2002","article-title":"Epstein-Barr virus latent membrane protein 2A regulates c-Jun protein through extracellular signal-regulated kinase","volume":"76","author":"Chen","year":"2002","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.virol.2003.09.017","article-title":"Epstein-Barr virus (EBV) LMP2A alters normal transcriptional regulation following B-cell receptor activation","volume":"318","author":"Portis","year":"2004","journal-title":"Virology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s12935-021-01793-3","article-title":"Signaling pathways of EBV-induced oncogenesis","volume":"21","author":"Luo","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Vrzalikova, K., Sunmonu, T., Reynolds, G., and Murray, P. (2018). Contribution of Epstein(-)Barr Virus Latent Proteins to the Pathogenesis of Classical Hodgkin Lymphoma. Pathogens, 7.","DOI":"10.3390\/pathogens7030059"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1476-4598-9-32","article-title":"EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1\/waf1 and a worse prognosis","volume":"9","author":"Liu","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0065-230X(10)07004-1","article-title":"Role of EBERs in the pathogenesis of EBV infection","volume":"107","author":"Iwakiri","year":"2010","journal-title":"Adv. Cancer Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s13027-020-00307-6","article-title":"Epstein-Barr virus BART microRNAs in EBV- associated Hodgkin lymphoma and gastric cancer","volume":"15","author":"Caggiari","year":"2020","journal-title":"Infect. Agent Cancer"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1002\/ijc.24502","article-title":"Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases","volume":"125","author":"Lake","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.cancergen.2016.08.006","article-title":"Karyotypic abnormalities associated with Epstein-Barr virus status in classical Hodgkin lymphoma","volume":"209","author":"Montgomery","year":"2016","journal-title":"Cancer Genet."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.pathol.4.110807.092209","article-title":"Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma","volume":"4","author":"Schmitz","year":"2009","journal-title":"Annu. Rev. Pathol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1002\/ijc.22511","article-title":"The aberrant coexpression of several receptor tyrosine kinases is largely restricted to EBV-negative cases of classical Hodgkin\u2019s lymphoma","volume":"120","author":"Hinsch","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1084\/jem.20090528","article-title":"TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma","volume":"206","author":"Schmitz","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.canlet.2015.10.007","article-title":"Microenvironmental interactions in classical Hodgkin lymphoma and their role in promoting tumor growth, immune escape and drug resistance","volume":"380","author":"Aldinucci","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"6379","DOI":"10.1200\/JCO.2005.55.013","article-title":"Molecular pathogenesis of Hodgkin\u2019s lymphoma","volume":"23","author":"Re","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1189\/jlb.3MR0315-136R","article-title":"The role of T cells in the microenvironment of Hodgkin lymphoma","volume":"99","author":"Wein","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1158\/2159-8290.CD-19-0680","article-title":"Single-Cell Transcriptome Analysis Reveals Disease-Defining T-cell Subsets in the Tumor Microenvironment of Classic Hodgkin Lymphoma","volume":"10","author":"Aoki","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e2105822118","DOI":"10.1073\/pnas.2105822118","article-title":"Single-cell profiling reveals the importance of CXCL13\/CXCR5 axis biology in lymphocyte-rich classic Hodgkin lymphoma","volume":"118","author":"Aoki","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1182\/blood-2018-04-843714","article-title":"Mass cytometry of Hodgkin lymphoma reveals a CD4(+) regulatory T-cell-rich and exhausted T-effector microenvironment","volume":"132","author":"Cader","year":"2018","journal-title":"Blood"},{"key":"ref_133","first-page":"912","article-title":"CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin\u2019s disease","volume":"147","author":"Carbone","year":"1995","journal-title":"Am. J. Pathol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1200\/JCO.2010.32.8401","article-title":"Molecular pathogenesis of Hodgkin\u2019s lymphoma: Increasing evidence of the importance of the microenvironment","volume":"29","author":"Steidl","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s41379-019-0254-4","article-title":"The pathological features of angioimmunoblastic T-cell lymphomas with IDH2(R172) mutations","volume":"32","author":"Steinhilber","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Kujala, J., Hartikainen, J.M., Tengstr\u00f6m, M., Sironen, R., Auvinen, P., Kosma, V.M., and Mannermaa, A. (2022). Circulating Cell-Free DNA Reflects the Clonal Evolution of Breast Cancer Tumors. Cancers, 14.","DOI":"10.3390\/cancers14051332"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.lungcan.2016.01.023","article-title":"Monitoring of treatment responses and clonal evolution of tumor cells by circulating tumor DNA of heterogeneous mutant EGFR genes in lung cancer","volume":"94","author":"Imamura","year":"2016","journal-title":"Lung Cancer"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1038\/nm.3870","article-title":"Clonal evolution and resistance to EGFR blockade in the blood of colorectal cancer patients","volume":"21","author":"Siravegna","year":"2015","journal-title":"Nat. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.pharmthera.2017.02.003","article-title":"Capturing tumor heterogeneity and clonal evolution in solid cancers using circulating tumor DNA analysis","volume":"174","author":"Perdigones","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"364ra155","DOI":"10.1126\/scitranslmed.aai8545","article-title":"Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA","volume":"8","author":"Scherer","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1182\/blood-2016-05-719641","article-title":"Diffuse large B-cell lymphoma genotyping on the liquid biopsy","volume":"129","author":"Rossi","year":"2017","journal-title":"Blood"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/13\/3222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:14Z","timestamp":1760139674000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/13\/3222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":141,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["cancers14133222"],"URL":"https:\/\/doi.org\/10.3390\/cancers14133222","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}