gms | German Medical Science

67th Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Korean Neurosurgical Society (KNS)

German Society of Neurosurgery (DGNC)

12 - 15 June 2016, Frankfurt am Main

Postsurgical molecular tumor analysis and liquid biopsy: A CNS-lymphoma pilot study analyzing cell-free tumor DNA

Meeting Abstract

  • Anne-Katrin Hickmann - Zentrum für Minimalinvasive und Endoskopische Neurochirurgie, Klinik Hirslanden, Zürich, Switzerland; Neurochirurgische Klinik, Klinikum Stuttgart, Stuttgart, Germany
  • Dennis Döcker - Center for Genomics and Transcriptomics (CeGaT GmbH), Tübingen, Germany
  • Gerald Illerhaus - Klinik für Hämatologie, Onkologie und Palliativmedizin, Klinikum Stuttgart, Stuttgart, Germany
  • Markus Bittl - Neurochirurgische Klinik, Klinikum Stuttgart, Stuttgart, Germany
  • Oliver Ganslandt - Neurochirurgische Klinik, Klinikum Stuttgart, Stuttgart, Germany
  • Saskia Biskup - Center for Genomics and Transcriptomics (CeGaT GmbH), Tübingen, Germany; Hertie-Institut für klinische Hirnforschung, Universität Tübingen, Tübingen, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocMI.10.07

doi: 10.3205/16dgnc288, urn:nbn:de:0183-16dgnc2888

Published: June 8, 2016

© 2016 Hickmann et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at



Objective: Usually, the diagnosis of metastasis and primary brain tumors has to be confirmed pathologically after invasive tissue biopsy. In central nervous system (CNS) lymphomas, stereotactic biopsy is mostly performed for diagnostic reasons. With the advent of novel technologies, less invasive diagnostic approaches – such as the analysis of cell-free tumor DNA (ctDNA, “liquid biopsy”) – have begun to revolutionize the “classic” approach. Our study aims to prove feasibility of minimally-invasive diagnostic approaches and establish a molecular characterization of CNS-lymphomas.

Method: Peripheral blood was taken as “control tissue” prior to surgery (open / stereotactic biopsy). Lumbar puncture was performed for routine pathologic and chemical cerebrospinal fluid (CSF) testing as well as molecular (CSF ctDNA) analysis. A second blood sample was taken at the time of surgery for molecular analysis (plasma ctDNA). We performed a next generation sequencing (NGS) somatic tumor panel (TUM01, >600 genes) of the biopsy tissue. The individual molecular somatic mutation pattern was used as basis for further characterization of ctDNA from plasma and CSF samples. Different approaches of further characterization (amplicon-based ultra-deep sequencing, digital PCR) were applied.

Results: For this clinical investigation 6 patients were recruited, all of which were female (mean age: 66.8 years). Primary CNS-lymphoma was pathologically confirmed in 5 cases (83.3 %). With routine pathologic analysis, lymphoma cells were identified in 2 CSF samples (33.3 %). The TUM01 panel combines ultra-deep NGS with the comparison of tumor vs. “normal” tissue, resulting in an extremely high analytic confidence. The biopsy tissue analysis revealed a specific somatic mutation pattern in all confirmed lymphoma samples (sensitivity 100 %), whereas no somatic mutations were detected in the sample that was identified as normal brain tissue (specificity 100 %). Somatic mutations were also detected in ctDNA samples.

Conclusions: Microscopic CSF analysis is unreliable for diagnosis of CNS-lymphomas. Stereotactic biopsy carries the risk of devastating complications. New approaches are warranted to reduce perioperative morbidity and mortality. This study proves feasibility of minimally-invasive approaches by analyzing ctDNA. Specific somatic mutation patterns could enable individualized monitoring of tumor diseases. In the future, molecular analyzes of ctDNA might replace invasive biopsies in certain tumor entities such as CNS-lymphoma.