Background: Brain tumors exhibit significant molecular heterogeneity, complicating diagnosis, prognosis, and treatment. Traditional tissue biopsies are invasive and often fail to capture the full tumor landscape due to intratumoral heterogeneity. Liquid biopsy, which analyzes cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA), offers a minimally invasive alternative for tumor profiling. Nanopore sequencing, a novel long-read sequencing technology, is emerging as a valuable tool in this context.

Purpose: This review explores the application of nanopore sequencing in molecular profiling of brain tumors using liquid biopsy, focusing on its ability to detect both genetic and epigenetic alterations with clinical relevance.

Main body: Brain tumors, such as gliomas and medulloblastomas, are characterized by diverse molecular profiles, which influence patient outcomes and treatment strategies. Nanopore sequencing offers unique advantages for profiling cfDNA from biofluids like cerebrospinal fluid (CSF) and plasma, including the ability to generate long reads and detect structural variants, copy number alterations, and methylation patterns. Several studies have demonstrated its potential to identify key mutations (e.g., IDH1/2, H3K27 M) and track tumor evolution through serial cfDNA monitoring. However, challenges remain, including low ctDNA fractions in biofluids and bioinformatic complexities.

Conclusion: Nanopore sequencing holds significant promise for advancing non-invasive molecular profiling of brain tumors, offering real-time insights into tumor genomics and evolution. This technology could revolutionize personalized brain tumor management, but further validation and optimization are needed before it can be routinely applied in clinical practice.

Nanopore Sequencing, Liquid Biopsy, Cell-Free DNA (cfDNA), Brain Tumor Profiling, Molecular Heterogeneity