Medulloblastoma is a type of cancer that affects the brain and spinal cord. Recent advances in long-read sequencing technology have enabled researchers to identify a broad spectrum of structural variants in cancer genomes that drive tumorigenesis. The study of paired diagnostic and post-therapy medulloblastoma samples using long-read sequencing technology revealed the haplotype-resolved somatic genetic and epigenetic landscape, including a 1.55 Megabasepair chromothripsis event, and a complex pattern of structural variants called "templated insertion thread". The study also performed long-read based methylome profiling, identifying allele-specific methylation effects, complex rearrangements with differential methylation, and differential promoter methylation in seven cancer-driver genes. Long-read sequencing technology has the potential to reveal new diagnostic and therapeutic targets in medulloblastoma and other cancers.