The whole-genome landscape of medulloblastoma subtypes

By P. Northcott, I. Buchhalter, A. Morrissy, V. Hovestadt, J. Weischenfeldt, T. Ehrenberger, Susanne N. Gröbner, M. Segura-Wang, T. Zichner, V. Rudneva and 77 more. Nature, 2017

956 citations recorded by the source corpus.

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and ‘enhancer hijacking’ events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/50072b665feb574e6550d0ee18e6e2d2d78e8038

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In Genetics

1. Peter W. Laird
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In Molecular Biology

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Citations in the corpus

• The landscape of genomic alterations across childhood cancers (2018, positive): “Cancer type-specific events that occurred together with high expression (data derived from Northcott et al. 44 ) included alterations of RIMS2 45 .”
• The chromatin accessibility landscape of primary human cancers (2018, result): “Consistent with published reports (12, 18, 29, 30), the degree of DNA methylation was anticorrelated with chromatin accessibility at regulatory elements, and regions lacking chromatin accessibilityweremore frequentlymethylated (fig.”