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Whole genome sequencing of tumour and normal paired samples of diffuse intrinsic pontine gliomas

Diffuse intrinsic pontine glioma (DIPG) have a universally dismal prognosis (median 9-12 months), with neither chemotherapeutic nor targeted agents showing any substantial survival benefit in clinical trials in children with these tumours. DIPG are highly infiltrative malignant glial neoplasms of the ventral pons, which due to their location within the brain, make them unsuitable for surgical resection and consequently have a universally dismal clinical outcome. Recent high-throughput sequencing approaches have revealed a striking prevalence of K27M mutations in the genes encoding the histone variants H3.3 (H3F3A) or H3.1 (HIST1H3B) in the childhood brain tumour DIPG. This K-to-M substitution confers a trans-dominant ablation of global H3K27 trimethylation, which likely profoundly alters gene expression through de-repression of polycomb repressive complex 2 (PRC2) target genes. Despite these advances in our understanding of the distinct biology of these tumours, approaches for specific novel therapeutic interventions are not clear, and little has been reported of the secondary mutations accompanying these changes. We carried out whole genome sequencing on a series of 20 tumour normal pairs of pre-treatment biopsy samples of DIPG, for which the patients underwent a safe stereotactic procedure, and whole exome sequencing on a further six tumour normal pairs obtained at autopsy.

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
EGAD00001000705 Illumina HiSeq 2000 40
EGAD00001000706 Illumina HiSeq 2000 12
Publications Citations
Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma.
Nat Genet 46: 2014 457-461
ATRX mutations and glioblastoma: Impaired DNA damage repair, alternative lengthening of telomeres, and genetic instability.
Mol Cell Oncol 3: 2016 e1167158
Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma.
Oncotarget 7: 2016 65696-65706
Identification of potentially oncogenic alterations from tumor-only samples reveals Fanconi anemia pathway mutations in bladder carcinomas.
NPJ Genom Med 2: 2017 29
Functional diversity and cooperativity between subclonal populations of pediatric glioblastoma and diffuse intrinsic pontine glioma cells.
Nat Med 24: 2018 1204-1215