A case of X-linked retinoschisis with atypical fundus appearance.

Authors

Nasser F1, Kohl S1, Kuehlewein L1, Wissinger B1, Obermaier CD2, Kurtenbach A1, Zrenner E1,3.
  1. Institute for Ophthalmic Research, Centre for Ophthalmology, Eberhard Karls University, Elfriede-Aulhorn Strasse 7, 72076, Tübingen, Germany
  2. CeGaT GmbH, Tuebingen, Germany.
  3. Werner Reichardt Center for Integrative Neuroscience, Eberhard Karls University, Tuebingen, Germany.

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.