Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Lymphoma

Genotyping circulating tumor DNA of pediatric Hodgkin lymphoma

Leukemia volume 34, pages 151–166 (2020)Cite this article

Subjects

Abstract

We used hybrid capture-targeted next-generation sequencing of circulating cell-free DNA (ccfDNA) of pediatric Hodgkin lymphoma (PHL) patients to determine pathogenic mechanisms and assess the clinical utility of this method. Hodgkin-Reed/Sternberg (HRS) cell-derived single nucleotide variants, insertions/deletions, translocations and VH-DH-JH rearrangements were detected in pretherapy ccfDNA of 72 of 96 patients. Number of variants per patient ranged from 1 to 21 with allele frequencies from 0.6 to 42%. Nine translocation breakpoints were detected. Genes involved in JAK/STAT, NFkB and PI3K signaling and antigen presentation were most frequently affected. SOCS1 variants, mainly deletions, were found in most circulating tumor (ct) DNAs, and seven of the nine translocation breakpoints involved SOCS1. Analysis of VH-DH-JH rearrangements revealed an origin of PHL HRS cells from partially selected germinal center B cells. Amounts of pretherapy ctDNA were correlated with metabolic tumor volumes. Furthermore, in all ccfDNA samples of 43 patients with early response assessment quantitative qPET < 3, indicative of a favorable clinical course, ctDNA was not detectable. In contrast, in five of six patients with qPET > 3, indicative of an unfavorable clinical course, ctDNA remained detectable. ccfDNA analysis of PHL is thus a suitable approach to determine pathogenic mechanisms and monitor therapy response.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Mauz-Korholz C, Metzger ML, Kelly KM, Schwartz CL, Castellanos ME, Dieckmann K. et al. Pediatric Hodgkin lymphoma. J Clin Oncol. 2015;33:2975–85.

    Article  PubMed  CAS  Google Scholar 

  2. Castellino SM, Geiger AM, Mertens AC, Leisenring WM, Tooze JA, Goodman P, et al. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study. Blood. 2011;117:1806–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dorffel W, Riepenhausenl M, Luders H, Bramswig J, Schellong G. Secondary malignancies following treatment for Hodgkin’s lymphoma in childhood and adolescence. Dtsch Arztebl Int. 2015;112:320–7. i

    PubMed  PubMed Central  Google Scholar 

  4. Schaapveld M, Aleman BM, van Eggermond AM, Janus CP, Krol AD, van der Maazen RW, et al. Second cancer risk up to 40 years after treatment for Hodgkin’s lymphoma. N Engl J Med. 2015;373:2499–511.

    Article  CAS  PubMed  Google Scholar 

  5. Barros MH, Hassan R, Niedobitek G. Tumor-associated macrophages in pediatric classical Hodgkin lymphoma: association with Epstein−Barr virus, lymphocyte subsets, and prognostic impact. Clin Cancer Res. 2012;18:3762–71.

    Article  CAS  PubMed  Google Scholar 

  6. Barros MH, Vera-Lozada G, Soares FA, Niedobitek G, Hassan R. Tumor microenvironment composition in pediatric classical Hodgkin lymphoma is modulated by age and Epstein−Barr virus infection. Int J Cancer. 2012;131:1142–52.

    Article  CAS  PubMed  Google Scholar 

  7. Wan JCM, Massie C, Garcia-Corbacho J, Mouliere F, Brenton JD, Caldas C, et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat Rev Cancer. 2017;17:223–38.

    Article  CAS  PubMed  Google Scholar 

  8. Kurtz DM, Green MR, Bratman SV, Scherer F, Liu CL, Kunder CA, et al. Noninvasive monitoring of diffuse large B-cell lymphoma by immunoglobulin high-throughput sequencing. Blood. 2015;125:3679–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Oberle A, Brandt A, Voigtlaender M, Thiele B, Radloff J, Schulenkorf A, et al. Monitoring multiple myeloma by next-generation sequencing of V(D)J rearrangements from circulating myeloma cells and cell-free myeloma DNA. Haematologica. 2017;102:1105–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Roschewski M, Dunleavy K, Pittaluga S, Moorhead M, Pepin F, Kong K, et al. Circulating tumour DNA and CT monitoring in patients with untreated diffuse large B-cell lymphoma: a correlative biomarker study. Lancet Oncol. 2015;16:541–9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Rossi D, Diop F, Spaccarotella E, Monti S, Zanni M, Rasi S, et al. Diffuse large B-cell lymphoma genotyping on the liquid biopsy. Blood. 2017;129:1947–57.

    Article  CAS  PubMed  Google Scholar 

  12. Scherer F, Kurtz DM, Newman AM, Stehr H, Craig AF, Esfahani MS. et al. Distinct biological subtypes and patterns of genome evolution in lymphoma revealed by circulating tumor DNA. Sci Transl Med. 2016;8:364ra155

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Bessi L, Viailly PJ, Bohers E, Ruminy P, Maingonnat C, Bertrand P, et al. Somatic mutations of cell-free circulating DNA detected by targeted next-generation sequencing and digital droplet PCR in classical Hodgkin lymphoma. Leuk Lymphoma. 2019;60:498–502.

    Article  CAS  Google Scholar 

  14. Camus V, Stamatoullas A, Mareschal S, Viailly PJ, Sarafan-Vasseur N, Bohers E, et al. Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma. Haematologica. 2016;101:1094–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Oki Y, Neelapu SS, Fanale M, Kwak LW, Fayad L, Rodriguez MA, et al. Detection of classical Hodgkin lymphoma specific sequence in peripheral blood using a next-generation sequencing approach. Br J Haematol. 2015;169:689–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Spina V, Bruscaggin A, Cuccaro A, Martini M, Di Trani M, Forestieri G, et al. Circulating tumor DNA reveals genetics, clonal evolution and residual disease in classical Hodgkin lymphoma. Blood. 2018;131:2413–25.

    Article  CAS  PubMed  Google Scholar 

  17. Vandenberghe P, Wlodarska I, Tousseyn T, Dehaspe L, Dierickx D, Verheecke M, 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:e55–65.

    Article  PubMed  Google Scholar 

  18. Hasenclever D, Kurch L, Mauz-Korholz C, Elsner A, Georgi T, Wallace H, et al. qPET—a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma. Eur J Nucl Med Mol Imaging. 2014;41:1301–8.

    Article  PubMed  Google Scholar 

  19. Bea S, Valdes-Mas R, Navarro A, Salaverria I, Martin-Garcia D, Jares P, et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci USA. 2013;110:18250–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Clipson A, Wang M, de Leval L, Ashton-Key M, Wotherspoon A, Vassiliou G, et al. KLF2 mutation is the most frequent somatic change in splenic marginal zone lymphoma and identifies a subset with distinct genotype. Leukemia. 2015;29:1177–85.

    Article  CAS  PubMed  Google Scholar 

  21. Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL, et al. Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. Blood. 2013;121:1604–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Green MR, Kihira S, Liu CL, Nair RV, Salari R, Gentles AJ, et al. Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation. Proc Natl Acad Sci USA. 2015;112:E1116–1125.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Guieze R, Robbe P, Clifford R, de Guibert S, Pereira B, Timbs A, et al. Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. Blood. 2015;126:2110–7.

    Article  CAS  PubMed  Google Scholar 

  24. Kiel MJ, Velusamy T, Betz BL, Zhao L, Weigelin HG, Chiang MY, et al. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med. 2012;209:1553–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kridel R, Meissner B, Rogic S, Boyle M, Telenius A, Woolcock B, et al. Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma. Blood. 2012;119:1963–71.

    Article  CAS  PubMed  Google Scholar 

  26. Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, Lawrence MS. et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell. 2013;152:714–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li H, Kaminski MS, Li Y, Yildiz M, Ouillette P, Jones S, et al. Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma. Blood. 2014;123:1487–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lohr JG, Stojanov P, Carter SL, Cruz-Gordillo P, Lawrence MS, Auclair D, et al. Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy. Cancer Cell. 2014;25:91–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Lohr JG, Stojanov P, Lawrence MS, Auclair D, Chapuy B, Sougnez C, et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci USA. 2012;109:3879–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Love C, Sun Z, Jima D, Li G, Zhang J, Miles R, et al. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet. 2012;44:1321–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Morin RD, Mungall K, Pleasance E, Mungall AJ, Goya R, Huff RD, et al. Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing. Blood. 2013;122:1256–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Okosun J, Bodor C, Wang J, Araf S, Yang CY, Pan C, et al. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet. 2014;46:176–81.

    Article  CAS  PubMed  Google Scholar 

  33. Pasqualucci L, Trifonov V, Fabbri G, Ma J, Rossi D, Chiarenza A, et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet. 2011;43:830–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Quesada V, Ramsay AJ, Lopez-Otin C. Chronic lymphocytic leukemia with SF3B1 mutation. N Engl J Med. 2012;366:2530.

    Article  CAS  PubMed  Google Scholar 

  35. Richter J, Schlesner M, Hoffmann S, Kreuz M, Leich E, Burkhardt B, et al. Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing. Nat Genet. 2012;44:1316–20.

    Article  CAS  PubMed  Google Scholar 

  36. Rossi D, Trifonov V, Fangazio M, Bruscaggin A, Rasi S, Spina V, et al. The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. J Exp Med. 2012;209:1537–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012;490:116–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011;365:2497–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhang J, Grubor V, Love CL, Banerjee A, Richards KL, Mieczkowski PA, et al. Genetic heterogeneity of diffuse large B-cell lymphoma. Proc Natl Acad Sci USA. 2013;110:1398–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhang J, Jima D, Moffitt AB, Liu Q, Czader M, Hsi ED, et al. The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells. Blood. 2014;123:2988–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Reichel J, Chadburn A, Rubinstein PG, Giulino-Roth L, Tam W, Liu Y, et al. Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood. 2015;125:1061–72.

    Article  CAS  PubMed  Google Scholar 

  42. Tiacci E, Penson A, Schiavoni G, Ladewig E, Fortini E, Wang Y, et al. New recurrently mutated genes in classical Hodgkin lymphoma revealed by whole-exome sequencing os microdissected tumor cells. Blood. 2016;218:1088.

    Article  Google Scholar 

  43. Raczy C, Petrovski R, Saunders CT, Chorny I, Kruglyak S, Margulies EH, et al. Isaac: ultra-fast whole-genome secondary analysis on Illumina sequencing platforms. Bioinformatics. 2013;29:2041–3.

    Article  CAS  PubMed  Google Scholar 

  44. Kuppers R, Dalla-Favera R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene. 2001;20:5580–94.

    Article  CAS  PubMed  Google Scholar 

  45. Martin-Subero JI, Klapper W, Sotnikova A, Callet-Bauchu E, Harder L, Bastard C, et al. Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. Cancer Res. 2006;66:10332–8.

    Article  CAS  PubMed  Google Scholar 

  46. Tiacci E, Ladewig E, Schiavoni G, Penson A, Fortini E, Pettirossi V, et al. Pervasive mutations of JAK-STAT pathway genes in classical Hodgkin lymphoma. Blood. 2018;131:2454–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mansouri L, Noerenberg D, Young E, Mylonas E, Abdulla M, Frick M, et al. Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma. Blood. 2016;128:2666–70.

    Article  CAS  PubMed  Google Scholar 

  48. Pasqualucci L, Neumeister P, Goossens T, Nanjangud G, Chaganti RS, Kuppers R, et al. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature. 2001;412:341–6.

    Article  CAS  PubMed  Google Scholar 

  49. Lennerz JK, Hoffmann K, Bubolz AM, Lessel D, Welke C, Ruther N, et al. Suppressor of cytokine signaling 1 gene mutation status as a prognostic biomarker in classical Hodgkin lymphoma. Oncotarget. 2015;6:29097–110.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Mottok A, Renne C, Willenbrock K, Hansmann ML, Brauninger A. Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6. Blood. 2007;110:3387–90.

    Article  CAS  PubMed  Google Scholar 

  51. Schif B, Lennerz JK, Kohler CW, Bentink S, Kreuz M, Melzner I, et al. SOCS1 mutation subtypes predict divergent outcomes in diffuse large B-Cell lymphoma (DLBCL) patients. Oncotarget. 2013;4:35–47.

    Article  PubMed  Google Scholar 

  52. Klein U, Goossens T, Fischer M, Kanzler H, Braeuninger A, Rajewsky K, et al. Somatic hypermutation in normal and transformed human B cells. Immunol Rev. 1998;162:261–80.

    Article  CAS  PubMed  Google Scholar 

  53. Sasanelli M, Meignan M, Haioun C, Berriolo-Riedinger A, Casasnovas RO, Biggi A, et al. Pretherapy metabolic tumour volume is an independent predictor of outcome in patients with diffuse large B-cell lymphoma. Eur J Nucl Med Mol Imaging. 2014;41:2017–22.

    Article  CAS  PubMed  Google Scholar 

  54. Tout M, Casasnovas O, Meignan M, Lamy T, Morschhauser F, Salles G, et al. Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report. Blood. 2017;129:2616–23.

    Article  CAS  PubMed  Google Scholar 

  55. Dukers DF, Meijer CJ, ten Berge RL, Vos W, Ossenkoppele GJ, Oudejans JJ. High numbers of active caspase 3-positive Reed-Sternberg cells in pretreatment biopsy specimens of patients with Hodgkin disease predict favorable clinical outcome. Blood. 2002;100:36–42.

    Article  CAS  PubMed  Google Scholar 

  56. Georgiadi EC, Sachinis N, Dimtsas G, Vassilakopoulos TP, Kittas C, Doussis-Anagnostopoulou IA. Evaluation of apoptosis in classical Hodgkin’s lymphoma comparing different methods. J BUON. 2012;17:746–52.

    CAS  PubMed  Google Scholar 

  57. Lorenzen J, Thiele J, Fischer R. The mummified Hodgkin cell: cell death in Hodgkin’s disease. J Pathol. 1997;182:288–98.

    Article  CAS  PubMed  Google Scholar 

  58. Kuppers R, Engert A, Hansmann ML. Hodgkin lymphoma. J Clin Invest. 2012;122:3439–47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Spina V, Bruscaggin A, Cuccaro A, Martini M, Di Trani M, Forestieri G, et al. Circulating tumor DNA reveals genetics, clonal evolution, and residual disease in classical Hodgkin lymphoma. Blood. 2018;131:2413–25.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We like to thank Annika Habbaba, Sebastian Schäfer, Cindy Arnold, Katharina Sack and Stefanie Rudloff for excellent technical assistance and Stefanie Avondstondt and Dieter Hoffmann from the Pediatric Hodgkin Lymphoma reference center for providing the clinical data documentation. The EuroNet-PHL-C2 trial is supported by a grant from the Deutsche Krebshilfe (Grant No.110674). This study was supported by the Deutsche Krebshilfe (Grant no. 111711), the Rhön Klinikum AG (RKA FL_21), the Elternverein für leukämie- und krebskranke Kinder Gießen and the Kinderkrebshilfe Oldtimer Markt Mainz.

Author information

Authors and Affiliations

  1. Institute of Pathology, Justus-Liebig-University, Giessen, Germany

    Ann-Kathrin Desch, Kristin Hartung, Alexander Brobeil, Roland Schmitz, Stefan Gattenlöhner & Andreas Bräuninger

  2. Department of Pediatric Oncology and Hematology, Justus-Liebig-University, Giessen, Germany

    Ante Botzen, Theresa Jox, Christine Mauz-Körholz & Dieter Körholz

  3. Hematology, Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany

    Mathias Rummel

  4. Clinic for Nuclear Medicine, University of Leipzig, Leipzig, Germany

    Lars Kurch, Thomas Georgi & Regine Kluge

  5. Pediatrics 5 (Oncology, Hematology, Immunology), Stuttgart Cancer Center, Klinikum Stuttgart-Olga Hospital, Stuttgart, Germany

    Stefan Bielack

  6. Clinic for Children München Schwabing, Technical University of Munich, Munich, Germany

    Stefan Burdach

  7. CCC München—Comprehensive Cancer Center and DKTK German Cancer Consortium Munich, Munich, Germany

    Stefan Burdach

  8. Clinic for Children and Adolescents, University of Rostock, Rostock, Germany

    Carl Friedrich Classen

  9. Clinic for Children and Adolescent Medicine, University of Schleswig-Holstein, Kiel, Germany

    Alexander Claviez

  10. Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany

    Klaus-Michael Debatin

  11. University Clinic for Children and Adolescents, Eberhard Karls University, Tübingen, Germany

    Martin Ebinger

  12. Clinic for Pediatrics, Charite, Berlin, Germany

    Angelika Eggert

  13. Pediatric Hematology, Oncology, Hemostasiology, University of Mainz, Mainz, Germany

    Jörg Faber

  14. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Christian Flotho

  15. University Childrens Hospital Augsburg, Swabian Childrens Cancer Center, Augsburg, Germany

    Michael Frühwald

  16. Clinic for Pediatric Oncology and Hematology, Saarland University, Homburg, Germany

    Norbert Graf

  17. Children Hematology and Oncology, Bethel, Bielefeld, Germany

    Norbert Jorch

  18. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany

    Udo Kontny

  19. Divison of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany

    Christof Kramm

  20. Department of Pediatric Oncology, Hematology and Immunology, Children´s Hospital and Hopp Children’s Tumor Center, Ruprecht-Karls-University, Heidelberg, Germany

    Andreas Kulozik

  21. Clinic for Children and Adolescent Medicine, Klinikum Karlsruhe, Karlsruhe, Germany

    Joachim Kühr

  22. Pediatric Hematology and Oncology, Medical University, Hannover, Germany

    Karl-Walter Sykora

  23. Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany

    Markus Metzler

  24. University Childrens Hospital, Department of Pediatrics and Pediatric Hematology/Oncology, Klinikum Oldenburg AöR, Oldenburg, Germany

    Hermann L. Müller

  25. Clinic for Pediatric Hematology and Oncology, Klinikum Kassel, Kassel, Germany

    Michaela Nathrath

  26. Pediatric Hematology and Oncology, Klinikum Mittelrhein, Koblenz, Germany

    Thomas Nüßlein

  27. General Pediatrics, Oncology and Hematology, Vestische Kinder und Jugendklinik Datteln, Witten/Herdecke University, Witten, Germany

    Michael Paulussen

  28. Pediatric Hematology and Oncology, Klinikum Bremen, Bremen, Germany

    Arnulf Pekrun

  29. Pediatric Hematology and Oncology, University of Duisburg-Essen, Essen, Germany

    Dirk Reinhardt

  30. Asklepios Children Clinic, St. Augustin, Sankt Augustin, Germany

    Harald Reinhard

  31. Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Münster, Germany

    Claudia Rössig

  32. Clinic for Children and Adolescent Medicine, Helios Klinikum Erfurt, Erfurt, Germany

    Axel Sauerbrey

  33. Pediatric Hematology and Oncology, University Children’s Hospital, Julius-Maximilians-University Medical Center, Würzburg, Germany

    Paul-Gerhardt Schlegel

  34. Clinic for Children and Adolescent Medicine, Klinikum Dortmund, Dortmund, Germany

    Dominik T. Schneider

  35. Cnopf´sche Children Clinic, Clinic Hallerwiese, Nürnberg, Germany

    Wolfram Scheurlen

  36. Clinic for Children, Hematology and Oncology, Helios Klinikum Berlin-Buch, Berlin, Germany

    Lothar Schweigerer

  37. Pediatric Oncology and Hematology, University of Cologne, Cologne, Germany

    Thorsten Simon

  38. Pediatric Hematology and Oncology, Technical University, Dresden, Germany

    Meinolf Suttorp

  39. Pediatric Hematology and Oncology, Otto-von-Guericke-University, Magdeburg, Germany

    Peter Vorwerk

  40. Medical Faculty, Martin-Luther University, Halle, Germany

    Christine Mauz-Körholz

Authors
  1. Ann-Kathrin Desch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kristin Hartung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ante Botzen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexander Brobeil
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mathias Rummel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lars Kurch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Thomas Georgi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Theresa Jox
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Stefan Bielack
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stefan Burdach
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Carl Friedrich Classen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alexander Claviez
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Klaus-Michael Debatin
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Martin Ebinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Angelika Eggert
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jörg Faber
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Christian Flotho
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Michael Frühwald
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Norbert Graf
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Norbert Jorch
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Udo Kontny
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Christof Kramm
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Andreas Kulozik
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Joachim Kühr
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Karl-Walter Sykora
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Markus Metzler
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Hermann L. Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Michaela Nathrath
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. Thomas Nüßlein
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Michael Paulussen
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Arnulf Pekrun
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Dirk Reinhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Harald Reinhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. Claudia Rössig
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. Axel Sauerbrey
    View author publications

    You can also search for this author in PubMed Google Scholar

  36. Paul-Gerhardt Schlegel
    View author publications

    You can also search for this author in PubMed Google Scholar

  37. Dominik T. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  38. Wolfram Scheurlen
    View author publications

    You can also search for this author in PubMed Google Scholar

  39. Lothar Schweigerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  40. Thorsten Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  41. Meinolf Suttorp
    View author publications

    You can also search for this author in PubMed Google Scholar

  42. Peter Vorwerk
    View author publications

    You can also search for this author in PubMed Google Scholar

  43. Roland Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  44. Regine Kluge
    View author publications

    You can also search for this author in PubMed Google Scholar

  45. Christine Mauz-Körholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  46. Dieter Körholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  47. Stefan Gattenlöhner
    View author publications

    You can also search for this author in PubMed Google Scholar

  48. Andreas Bräuninger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas Bräuninger.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Desch, AK., Hartung, K., Botzen, A. et al. Genotyping circulating tumor DNA of pediatric Hodgkin lymphoma. Leukemia 34, 151–166 (2020). https://doi.org/10.1038/s41375-019-0541-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41375-019-0541-6

This article is cited by

Search

Advanced search

Quick links