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Single-cell study of 14 childhood medulloblastoma patients

Type: Whole Genome Sequencing
Archiver: European Genome-Phenome Archive (EGA)

1 Dataset 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001009057	Medulloblastoma intra-tumoural genetic heterogeneity and clonal evolution, and their role in disease pathogenesis and clinical behaviour, are poorly understood. We used single-cell whole-genome sequencing (sc-WGS) to reconstruct the natural history and temporal evolution of 14 medulloblastomas, representing its major clinico-molecular sub-classes. We identified wholly-clonal tumours which displayed single-clone expansion (i.e. linear evolution); all were observed in favourable-outcome sub-classes (i.e. MBWNT and infant MBSHH). In contrast, remaining tumours harboured sub-clonal structures which displayed punctuated or gradual trajectories; highest-risk sub-classes, typically characterised by MYC-amplification (MBGroup3) or TP53-mutation (MBSHH), and linked to genomic instability and LCA pathology, were most clonally-diverse. Clinically-adopted biomarkers were typically early-clonal/initiating events, representing exploitable targets for early-disease detection; in analyses of spatially-distinct tumour regions, a single biopsy was sufficient to assess their status. sc-WGS revealed events not previously appreciated in bulk tumour analysis, which arose later and/or sub-clonally and more commonly displayed spatial diversity; their clinical significance and role in disease evolution post-diagnosis now require establishment. In summary, our findings reveal diverse modes of tumour initiation and clonal evolution in the major medulloblastoma sub-classes, highlighting their pathogenic relevance and clinical potential.	NextSeq 500	430

Publications	Citations
Single-cell DNA sequencing identifies risk-associated clonal complexity and evolutionary trajectories in childhood medulloblastoma development. Danilenko M, Zaka M, Keeling C, Crosier S, Lyman S, Finetti M, Williamson D, Hussain R, Coxhead J, Zhou P, Hill RM, Hicks D, Rand V, Joshi A, Schwalbe EC, Bailey S, Clifford SC. Acta Neuropathol 144: 2022 565-578	2