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

Project description: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 [DNA methylation EPIC]

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

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Longitudinal Performance of Epi proColon

Project description:This study will evaluate longitudinal performance of Epi proColon with respect to test positivity, longitudinal adherence to Epi proColon screening, adherence to follow-up colonoscopy and diagnostic yield, as well as assay failure rates.

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Characteristics PDX

Project description:Characteristics PDX

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Gene Expression data from Pdx-1CreAPC+/LP53L/L pancreatic ductal adenocarcinoma (PDAC) cells versus Pdx-1CreP53L/L normal pancreatic ductal cells

Project description:Analysis of primary PDAC cells established from Pdx-1CreAPCL/+p53L/L and Pdx-1Crep53L/L mice. APC haploinsufficiency combined with P53 loss in the pancreas drives MCN progression in mice. Results provide insight into molecular mechanisms invloved in the MCN formation of Pdx-1Cre APCL/+P53L/L mice. Pdx-1CreAPC+/LP53L/L PDAC cell lines and 2 Pdx-1CreP53L/L ductal cell lines were analyzed.

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Comparison of transcriptome profile between wild-type and Epi-df mutant plants

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Genetic control of yeast chromatin acetylation epi-polymorphisms

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