Longitudinal multi-omics characterization of the malignant evolution in multirelapsing glioblastoma

The study tracked glioblastoma (brain cancer) progression in a single patient over 31 months through 11 surgical procedures and sample collection from multiple sites, including terminal leptomeningeal spread. All samples shared mutations in RB1 and NF1 genes, while advanced disease stages and extracranial metastases featured mutations in TSC2, PBRM1, CD22, and FANCI genes. These mutations were associated with resistance to immunotherapies and DNA-damaging treatments. Single-cell analysis revealed reversible changes in response to treatment. The study documents glioblastoma evolution over an unusually long time period and links genetic, molecular, cellular, and clinical aspects of disease progression.