a, Copy-neutral LOH PTCH1−/− driver status reverts to wild type post-therapy in medulloblastoma-REC-12, with homozygous CDKN2A/B loss. b, The evolutionary progression of medulloblastoma-REC-12 is illustrated by (pink) PTCH1+/− lineage expansion, copy-neutral LOH, clonal eradication during treatment, and (blue) subsequent expansion of an ancestral clone with CDKN2A/B−/−. c, Phylogenetic relationships between primary (red) and recurrent (blue) tumours show that recurrences often represent a single rather than multiple primary tumour lineages (for example, medulloblastoma-REC-05/12 compared with medulloblastoma-REC-02). d, Ultra-deep sequencing shows post-treatment expansion of low-frequency or de novo primary clones (blue), and eradication/reduction of therapy-sensitive lineages (red). Inset box indicates number of mutations per cluster.