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- Title
Molecular tumor analysis and liquid biopsy: a feasibility investigation analyzing circulating tumor DNA in patients with central nervous system lymphomas.
- Authors
Hickmann, Anne-Katrin; Frick, Maximilian; Hadaschik, Dirk; Battke, Florian; Bittl, Markus; Ganslandt, Oliver; Biskup, Saskia; Döcker, Dennis
- Abstract
<bold>Background: </bold>Central nervous system lymphomas (CNSL) is a devastating disease. Currently, a confirmatory biopsy is required prior to treatment.<bold>Objective: </bold>Our investigation aims to prove the feasibility of a minimally-invasive diagnostic approach for the molecular characterization of CNSL.<bold>Methods: </bold>Tissue biopsies from 6 patients with suspected CNSL were analyzed using a 649gene next-generation sequencing (NGS) tumor panel (tumor vs. reference tissue (EDTA-blood)). The individual somatic mutation pattern was used as a basis for the digital PCR analyzing circulating tumor DNA (ctDNA) from plasma and cerebrospinal fluid (CSF) samples, identifying one selected tumor mutation during this first step of the feasibility investigation.<bold>Results: </bold>NGS-analysis of biopsy tissue revealed a specific somatic mutation pattern in all confirmed lymphoma samples (n = 5, NGS-sensitivity 100%) and none in the sample identified as normal brain tissue (NGS-specificity 100%). cfDNA-extraction was dependent on the extraction-kit used and feasible in 3 samples, in all of which somatic mutations were detectable (100%). Analysis of CSF-derived cfDNA was superior to plasma-derived cfDNA and routine microscopic analysis (lymphoma cells: n = 2, 40%). One patient showed a divergent molecular pattern, typical of Burkitt-Lymphoma (HIV+, serologic evidence of EBV-infection). Lumbar puncture was tolerated without complications, whereas biopsy caused 3 hemorrhages.<bold>Conclusions: </bold>Our investigation provides evidence that analysis of cfDNA in central nervous system tumors is feasible using the described protocol. Molecular characterization of CNSL could be achieved by analysis of CSF-derived cfDNA. Knowledge of a tumor's specific mutation pattern may allow initiation of targeted therapies, treatment surveillance and could lead to minimally-invasive diagnostics in the future.
- Subjects
CIRCULATING tumor DNA; CENTRAL nervous system; CENTRAL nervous system tumors; SOMATIC mutation; CEREBROSPINAL fluid; LIQUID analysis
- Publication
BMC Cancer, 2019, Vol 19, Issue 1, p1
- ISSN
1471-2407
- Publication type
journal article
- DOI
10.1186/s12885-019-5394-x