Skip to main content
Medline Book to support NIHPA logoLink to Medline Book to support NIHPA
. 2022;2453:101–117. doi: 10.1007/978-1-0716-2115-8_7

cfDNA-Based NGS IG Analysis in Lymphoma.

Christiane Pott, Michaela Kotrova, Nikos Darzentas, Monika Brüggemann, Mouhamad Khouja; EuroClonality-NGS Working Group
PMCID: PMC9761545  PMID: 35622323

Abstract

Liquid biopsy is a novel diagnostic approach at first developed to characterize the molecular profile of solid tumors by analyzing body fluids. For cancer patients, it represents a noninvasive way to monitor the status of the solid tumor with respect to representative biomarkers. There is growing interest in the utilization of circulating tumor DNA (ctDNA) analysis also in the diagnostic and prognostic fields of lymphomas. Clonal immunoglobulin (IG) gene rearrangements are fingerprints of the respective lymphoid malignancy and thus are highly suited as specific molecular targets for minimal residual disease (MRD) detection. Tracing of the clonal IG rearrangement patterns in ctDNA pool during treatment can be used for MRD assessment in B-cell lymphomas. Here, we describe a reproducible next-generation sequencing assay to identify and characterize clonal IG gene rearrangements for MRD detection in cell-free DNA.


Full text of this article can be found in Bookshelf.

References

  1. Volckmar A-L, Sültmann H, Riediger A, Fioretos T, Schirmacher P, Endris V et al (2018) A field guide for cancer diagnostics using cell-free DNA: from principles to practice and clinical applications. Genes Chromosom Cancer 57:123–139 doi: 10.1002/gcc.22517. [DOI] [PubMed]
  2. Li Y, Pan W, Connolly ID, Reddy S, Nagpal S, Quake S et al (2016) Tumor DNA in cerebral spinal fluid reflects clinical course in a patient with melanoma leptomeningeal brain metastases. J Neuro-Oncol 128:93–100 doi: 10.1007/s11060-016-2081-5. [DOI] [PMC free article] [PubMed]
  3. Pan W, Gu W, Nagpal S, Hayden Gephart M, Quake SR (2015) Brain tumor mutations detected in cerebral spinal fluid. Clin Chem 61:514–522 doi: 10.1373/clinchem.2014.235457. [DOI] [PMC free article] [PubMed]
  4. Swinkels DW, de Kok JB, Hanselaar A, Lamers K, Boerman RH (2000) Early detection of leptomeningeal metastasis by PCR examination of tumor-derived K-ras DNA in cerebrospinal fluid. Clin Chem 46:132–133 [PubMed]
  5. Salvi S, Gurioli G, Martignano F, Foca F, Gunelli R, Cicchetti G et al (2015) Urine cell-free DNA integrity analysis for early detection of prostate cancer patients. Dis Markers 2015:574120 doi: 10.1155/2015/574120. [DOI] [PMC free article] [PubMed]
  6. Xia Y, Huang CC, Dittmar R, Du M, Wang Y, Liu H et al (2016) Copy number variations in urine cell free DNA as biomarkers in advanced prostate cancer. Oncotarget 7:35818–35831 doi: 10.18632/oncotarget.9027. [DOI] [PMC free article] [PubMed]
  7. Leon SA, Shapiro B, Sklaroff DM, Yaros MJ (1977) Free DNA in the serum of cancer patients and the effect of therapy. Cancer Res 37:646–650 [PubMed]
  8. van Dongen JJM, Langerak AW, Brüggemann M, Evans PA, Hummel M, Lavender FL et al (2003) 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. Leukemia 17:2257–2317 doi: 10.1038/sj.leu.2403202. [DOI] [PubMed]
  9. González D, González M, Alonso ME, Lopez-Perez R, Balanzategui A, Chillon MC et al (2003) Incomplete DJH rearrangements as a novel tumor target for minimal residual disease quantitation in multiple myeloma using real-time PCR. Leukemia 17:1051–1057 doi: 10.1038/sj.leu.2402937. [DOI] [PubMed]
  10. Langerak AW, Nadel B, de Torbal A, Wolvers-Tettero ILM, Van Gastel-Mol EJ, Verhaaf B et al (2004) Unraveling the consecutive recombination events in the human IGK locus. J Immunol 173:3878–3888 doi: 10.4049/jimmunol.173.6.3878. [DOI] [PubMed]
  11. Scheijen B, Meijers RWJ, Rijntjes J, van der Klift MY, Möbs M, Steinhilber J et al (2019) Next-generation sequencing of immunoglobulin gene rearrangements for clonality assessment: a technical feasibility study by EuroClonality-NGS. Leukemia 33:2227–2240 doi: 10.1038/s41375-019-0508-7. [DOI] [PMC free article] [PubMed]
  12. Knecht H, Reigl T, Kotrová M, Appelt F, Stewart P, Bystry V et al (2019) Quality control and quantification in IG/TR next-generation sequencing marker identification: protocols and bioinformatic functionalities by EuroClonality-NGS. Leukemia 33:2254–2265 doi: 10.1038/s41375-019-0499-4. [DOI] [PMC free article] [PubMed]
  13. Bystry V, Reigl T, Krejci A, Demko M, Hanakova B, Grioni A et al (2017) ARResT/interrogate: an interactive immunoprofiler for IG/TR NGS data. Bioinformatics 33:435–437 doi: 10.1093/bioinformatics/btw634. [DOI] [PubMed]
  14. Devonshire AS, Whale AS, Gutteridge A, Jones G, Cowen S, Foy CA et al (2014) Towards standardisation of cell-free DNA measurement in plasma: controls for extraction efficiency, fragment size bias and quantification. Anal Bioanal Chem 406:6499–6512 doi: 10.1007/s00216-014-7835-3. [DOI] [PMC free article] [PubMed]

RESOURCES