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A novel Induced-recurrence PDX model recapitulates epi-genomic features of Glioblastoma recurrence [RNA-seq]

ABSTRACT: A novel Induced-recurrence PDX model recapitulates epi-genomic features of Glioblastoma recurrence [RNA-seq]

PROVIDER: PRJNA1132515 | ENA |

REPOSITORIES: ENA

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			Action	DRS
		Other
	SRR29740900_1.fastq.gz	Fastqsanger.gz
	SRR29740900_2.fastq.gz	Fastqsanger.gz
	SRR29740901_1.fastq.gz	Fastqsanger.gz
	SRR29740901_2.fastq.gz	Fastqsanger.gz

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A novel Induced-recurrence PDX model recapitulates epi-genomic features of Glioblastoma recurrence [scRNA-seq]

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A novel Induced-recurrence PDX model recapitulates epi-genomic features of Glioblastoma recurrence [RNA-seq]

Project description:Glioblastoma remains incurable and, due to its infiltrative growth, high levels of treatment resistance and population of glioma initiating/stem cells (GICs), recurs in all patients. Here we design and characterize a novel induced-recurrence model in which mice xenografted with primary patient-derived GICs are treated with a therapeutic regimen closely recapitulating patient standard of care, followed by monitoring until tumours recur (IR-PDX). By tracking in vivo tumour growth, we confirm the patient specificity and initial efficacy of treatment prior to recurrence. Availability of longitudinally matched pairs of primary and recurrent GICs enabled patient-specific evaluation of the faithfulness with which the model recapitulated phenotypes associated with the true recurrence. Through comprehensive multi-omic analyses, we showed that the IR-PDX model recapitulated genomic, epigenetic, and transcriptional state heterogeneity changes upon recurrence in a patient-specific manner. The accuracy of the IR-PDX enabled both novel biological insights, including the positive association between glioblastoma recurrence and levels of ciliated neural stem cell-like tumour cells, and the identification of druggable patient-specific therapeutic vulnerabilities. This proof-of-concept study opens the possibility for prospective precision medicine approaches, in which the IR-PDX model is developed between first diagnosis and disease progression to identify target-drug candidates for use as second line of treatment at recurrence.

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