Featured
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Article |
Unified rhombic lip origins of group 3 and group 4 medulloblastoma
Multi-omic mapping shows that group 3 and group 4 medulloblastomas have a common, human-specific developmental origin in the cerebellar rhombic lip, providing a basis for their ambiguous molecular features and overlapping anatomical location, and for the difficulty of modelling these tumours in mice.
- Kyle S. Smith
- , Laure Bihannic
- & Paul A. Northcott
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Article |
Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma
Highly recurrent hotspot r.3A>G mutations are identified in U1 splicesomal small nuclear RNAs in about 50% of Sonic hedgehog medulloblastomas, which result in disrupted RNA splicing and the activation of oncogenes.
- Hiromichi Suzuki
- , Sachin A. Kumar
- & Michael D. Taylor
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Article |
Resolving medulloblastoma cellular architecture by single-cell genomics
Characterization of medulloblastoma tissues using single-cell transcriptomics shows that the different molecular subtypes consist of distinct developmental phenotypes.
- Volker Hovestadt
- , Kyle S. Smith
- & Paul A. Northcott
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Letter |
Recruitment of BRCA1 limits MYCN-driven accumulation of stalled RNA polymerase
In human neuroblastoma tumours, MYCN is engaged in a USP11–BRCA1-dependent manner to suppress the accumulation of stalled RNAPII and induces both the activation and repression of genes.
- Steffi Herold
- , Jacqueline Kalb
- & Martin Eilers
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Letter |
EWS–FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma
The EWS–FLI1 fusion protein, expressed in Ewing sarcoma, increases global transcription, causes accumulation of R loops and replication stress, and impairs BRCA1-mediated repair.
- Aparna Gorthi
- , July Carolina Romero
- & Alexander J. R. Bishop
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Article
| Open AccessThe landscape of genomic alterations across childhood cancers
Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.
- Susanne N. Gröbner
- , Barbara C. Worst
- & Stefan M. Pfister
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Article |
Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma
Disparate modes of suppression of the let-7 microRNA family are selectively and inversely related in neuroblastoma.
- John T. Powers
- , Kaloyan M. Tsanov
- & George Q. Daley
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Article |
Active medulloblastoma enhancers reveal subgroup-specific cellular origins
Genomic studies of the paediatric brain tumour medulloblastoma have revealed four clinically distinct molecular subgroups; here active gene regulatory elements in 28 primary medulloblastoma tissues are mapped to reveal differentially regulated enhancers across the different subgroups, allowing insights into the transcription factors that characterize subgroup divergence and the cellular origin of the poorly characterized Group 3 and 4 subgroups.
- Charles Y. Lin
- , Serap Erkek
- & Paul A. Northcott
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Article |
Divergent clonal selection dominates medulloblastoma at recurrence
To address the question of whether a recurrent tumour is genetically similar to the tumour at diagnosis, the evolution of medulloblastoma has been studied in both an in vivo mouse model of clinical tumour therapy as well as in humans with recurrent disease; targeted tumour therapies are usually based on targets present in the tumour at diagnosis but the results from this study indicate that post-treatment recurring tumours (compared with the tumour at diagnosis) have undergone substantial clonal divergence of the initial dominant tumour clone.
- A. Sorana Morrissy
- , Livia Garzia
- & Michael D. Taylor
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Letter |
Telomerase activation by genomic rearrangements in high-risk neuroblastoma
Activation of telomere maintenance mechanisms—caused by novel somatic rearrangements of TERT, by MYCN amplification, or ATRX mutations—is a hallmark of high-risk neuroblastomas.
- Martin Peifer
- , Falk Hertwig
- & Matthias Fischer
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Outlook |
Prevention: Air of danger
Carcinogens are all around us, so scientists are broadening their ideas of environmental risk.
- Rebecca Kessler
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Letter |
Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing
Medulloblastoma is a malignant childhood brain tumour presenting major clinical challenges; here, a comprehensive genome-wide DNA methylation data set from human and mouse tumours, coupled with analysis of histone modifications, RNA transcripts and genome sequencing, uncovers a wealth of alterations that provide insights into the epigenetic regulation of transcription and genome organization in medulloblastoma pathogenesis.
- Volker Hovestadt
- , David T. W. Jones
- & Peter Lichter
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Letter |
BAF complexes facilitate decatenation of DNA by topoisomerase IIα
Mutations in the subunits of BAF chromatin-remodelling complexes are frequently found in human cancer; here deletion of BAF subunits or expression of mutants of the ATPase subunit BRG1 attenuates genome-wide binding of topoisomerase IIα, resulting in tangled chromosomes, anaphase bridges and G2/M arrest.
- Emily C. Dykhuizen
- , Diana C. Hargreaves
- & Gerald R. Crabtree
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Letter
| Open AccessDissecting the genomic complexity underlying medulloblastoma
Medulloblastoma is the most common brain tumour in children; using whole-genome sequencing of tumour samples the authors show that the clinically challenging Group 3 and 4 tumours can be tetraploid, and reveal the expression of the first medulloblastoma fusion genes identified.
- David T. W. Jones
- , Natalie Jäger
- & Peter Lichter
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Letter |
Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma
Recurrent histone mutations are linked to paediatric glioblastoma multiforme, an aggressive type of brain tumour.
- Jeremy Schwartzentruber
- , Andrey Korshunov
- & Nada Jabado