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.
- Type: Other
- Archiver: European Genome-Phenome Archive (EGA)
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 |
118 |
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 |
194 |
YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis.
Nat Commun 10: 2019 3914 |
52 |
3D genome mapping identifies subgroup-specific chromosome conformations and tumor-dependency genes in ependymoma.
Nat Commun 14: 2023 2300 |
1 |