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Single-cell DNA sequencing identifies risk-associated clonal complexity and evolutionary trajectories in childhood medulloblastoma development.
- Source :
-
Acta Neuropathologica . Sep2022, Vol. 144 Issue 3, p565-578. 14p. - Publication Year :
- 2022
-
Abstract
- We reconstructed the natural history and temporal evolution of the most common childhood brain malignancy, medulloblastoma, by single-cell whole-genome sequencing (sc-WGS) of tumours representing its major molecular sub-classes and clinical risk groups. Favourable-risk disease sub-types assessed (MBWNT and infant desmoplastic/nodular MBSHH) typically comprised a single clone with no evidence of further evolution. In contrast, highest risk sub-classes (MYC-amplified MBGroup3 and TP53-mutated MBSHH) were most clonally diverse and displayed gradual evolutionary trajectories. Clinically adopted biomarkers (e.g. chromosome 6/17 aberrations; CTNNB1/TP53 mutations) were typically early-clonal/initiating events, exploitable as targets for early-disease detection; in analyses of spatially distinct tumour regions, a single biopsy was sufficient to assess their status. Importantly, sc-WGS revealed novel events which arise later and/or sub-clonally and more commonly display spatial diversity; their clinical significance and role in disease evolution post-diagnosis now require establishment. These findings reveal diverse modes of tumour initiation and evolution in the major medulloblastoma sub-classes, with pathogenic relevance and clinical potential. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00016322
- Volume :
- 144
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Acta Neuropathologica
- Publication Type :
- Academic Journal
- Accession number :
- 158546599
- Full Text :
- https://doi.org/10.1007/s00401-022-02464-x