Molecular tumor analysis and liquid biopsy: a feasibility investigation analyzing circulating tumor DNA in patients with central nervous system lymphomas.
BMC Cancer
; 19(1): 192, 2019 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-30823914
ABSTRACT
BACKGROUND:
Central nervous system lymphomas (CNSL) is a devastating disease. Currently, a confirmatory biopsy is required prior to treatment.OBJECTIVE:
Our investigation aims to prove the feasibility of a minimally-invasive diagnostic approach for the molecular characterization of CNSL.METHODS:
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.RESULTS:
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.CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Linfoma de Células B
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ADN Tumoral Circulante
Tipo de estudio:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
Límite:
Adult
/
Aged
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
BMC Cancer
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Suiza