Nanopore-based brain tumour classification: the harbinger of near-patient, ultra-rapid tumour sequencing

Abstract

Advances in both our understanding of tumour biology and our technological capacity to interrogate these molecular characteristics have led to the ever-increasing use of genomic sequencing in routine diagnostic decision making, long offering the hope of more efficacious personalized cancer therapies. Yet, despite this fidelity, in order that genomic testing is truly able to deliver its promise of better outcomes for patients, it is vital that such testing can be performed within a clinically relevant timeframe. Presently, molecular diagnosis of brain tumours is largely delivered via an effectively centralized model as few institutes possess the necessary facilities. Yet, this approach has inherent delays that mean a wait, often of several weeks, before the diagnosis is available to the treating clinical team. This review introduces Nanopore sequencing, a long-read technology that can be used to enable rapid and comprehensive molecular diagnosis. The epigenetic signatures of brain tumours have been shown to reliably segregate tumour subtypes, and methylation-based tumour classification now forms a cornerstone of neuropathological diagnosis. Crucially, Nanopore is a direct-strand sequencing technology which can detect methyl DNA modifications, alongside base-calling, delivering methylation classification in parallel with copy number, fusion and mutation detection as well as single gene methylation analysis. This review summarises the present state of nanopore sequencing for brain tumour diagnostics and highlights areas for further development.