PATH-64. COMPREHENSIVE CNS TUMOUR MOLECULAR DIAGNOSTICS USING THIRD GENERATION SEQUENCING

• DOI: 10.1093/neuonc/noad179.0693
• Publication Date: 2023-11-11T23:35:54Z
• Authors: Areeba Patel; Felix Hinz; Helin Dogan; Kirsten Goebel; Daniel Schrimpf; Pauline Goeller; Michael Ritter; Lisa Pfeifer; Christina Blume; Natalie Berghaus; Alexander Payne; Violaine Goidts; Matthew Loose; Andreas Unterberg; Wolfgang Wick; Stefan Pfister; Martin Sill; Andreas von Deimling; David Jones; Matthias Schlesner; Felix Sahm
• Keywords: Turnaround time; Indel; Subtyping; Concordance

Abstract The WHO classification of CNS tumours 2021 recommends reporting a wide range molecular alterations for WHO-compatible diagnoses. Conventional workflows warrant considerable investment and long turnaround times limited by batching. Nanopore sequencing enables read sequencing, real-time targeting simultaneous base modification detection with compact devices. Rapid-CNS2- rapid, comprehensive adaptive sampling based pipeline time 5 days was previously described. ad-hoc methylation model employed Rapid-CNS2 is to MNP v11 classes. This study presents an optimised validation cohort that successfully reports hard-to-detect variants. We also present whole genome workflow affords direct upload the website v12 classification. sequenced analysed 156 samples from Department Neuropathology, University Hospital Heidelberg using Rapid-CNS2. RESULTS: were compared NGS panel array analyses. showed improved resolution over CNAs. High accuracy obtained SNV/Indels. Long reads spanning breakpoint identified clinically relevant fusions in 10/10 cases. Subclonal SVs like EGFR vIII missed detected high confidence. Complete concordance achieved MGMT promoter status optimized shortened 30 hours sample receipt minimum input DNA required reduced 500ng. For WGS, 72h on Promethion device. WGS enabled accurate SNVs, CNAs, SVs, addition directly eliminating need training models. presented nanopore provide feasible single assay alternatives conventional diagnostic approaches aim make such analyses more accessible.