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Therapeutic Targeting of Ependymoma as Informed by Oncogenic Enhancer Profiling

Genomic sequencing has driven precision-based oncology therapy; however, genetic drivers remain unknown or non-targetable for many malignancies, demanding alternative approaches to identify therapeutic leads. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Here, we mapped active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts. Enhancer regions revealed novel oncogenes, molecular targets, and pathways, which when subjected to small molecule inhibitor or shRNA treatment, increased survival and slowed proliferation in mouse and neurosphere patient-derived models of ependymomas. This study represents one of the largest enhancer mapping study of any cancer type to date, and provides a framework for target and drug discovery for other cancers recalcitrant to therapeutic development because of their lack of known genetic drivers.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003940 Illumina HiSeq 2000 48
EGAD00001003966 Illumina HiSeq 2000 24
EGAD00001003973 Illumina HiSeq 2000 -
EGAD00001003979 Illumina HiSeq 2000 -
EGAD00001008801 Illumina NovaSeq 6000 14
EGAD00001008805 Illumina HiSeq 2000 1
EGAD00001008806 Illumina HiSeq 2000 1
Publications Citations
Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling.
Nature 553: 2018 101-105
116
InTAD: chromosome conformation guided analysis of enhancer target genes.
BMC Bioinformatics 20: 2019 60
8
Childhood cerebellar tumours mirror conserved fetal transcriptional programs.
Nature 572: 2019 67-73
186
YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis.
Nat Commun 10: 2019 3914
51
3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma.
Nat Commun 14: 2023 2300
1