58055c9a-c406-4e37-92f0-6ef7bdbba18e - samples
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ABSTRACT:
PROVIDER: EGAD00001009741 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Two primary tumor-derived PDAC organoids were subjected to SNP array, RNA-seq, and single-cell WGS
| EGAD00010002408 | EGA
Project description:We evaluated linked-read whole genome sequencing (WGS) for detection of structural chromosomal rearrangements in primary samples of varying DNA quality from 12 patients diagnosed with ALL. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements, aneuploidy assessment and gene deletions. Additional RNA-sequencing and copy number aberrations (CNA) data from Illumina Infinium arrays were also generated and assessed against the linked-read WGS data. RNA-sequencing data was used to support structural chromosomal rearrangements detected in the linked-read WGS data by detecting expressed fusion genes as a consequence of the rearrangements. Illumina Infinium arrays (450k array and/or SNP array) were used to assess CNA status to further support the findings in the linked-read WGS data. The processed CNA data from the primary ALL patient samples has been deposited to GEO. RNA-sequencing, linked-read WGS data, and raw SNP array data from the primary ALL patient samples will not be deposited because the patient/parent consent does not cover depositing data that may be used for large-scale determination of germline variants in a repository. The ALL samples were collected 10-20 years ago from pediatric patients aged 2-15 years, some whom have deceased. The linked-read WGS data and the RNA-sequencing data sets generated in the study are available upon reasonable request from the corresponding author Jessica.Nordlund@medsci.uu.se.
2020-03-02 | GSE116057 | GEO
Project description:We evaluated linked-read whole genome sequencing (WGS) for detection of structural chromosomal rearrangements in primary samples of varying DNA quality from 12 patients diagnosed with ALL. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements, aneuploidy assessment and gene deletions. Additional RNA-sequencing and copy number aberrations (CNA) data from Illumina Infinium arrays were also generated and assessed against the linked-read WGS data. RNA-sequencing data was used to support structural chromosomal rearrangements detected in the linked-read WGS data by detecting expressed fusion genes as a consequence of the rearrangements. Illumina Infinium arrays (450k array and/or SNP array) were used to assess CNA status to further support the findings in the linked-read WGS data. The processed CNA data from the primary ALL patient samples has been deposited to GEO. RNA-sequencing, linked-read WGS data, and raw SNP array data from the primary ALL patient samples will not be deposited because the patient/parent consent does not cover depositing data that may be used for large-scale determination of germline variants in a repository. The ALL samples were collected 10-20 years ago from pediatric patients aged 2-15 years, some whom have deceased. The linked-read WGS data and the RNA-sequencing data sets generated in the study are available upon reasonable request from the corresponding author Jessica.Nordlund@medsci.uu.se.
2020-03-02 | GSE117693 | GEO
Project description:We evaluated linked-read whole genome sequencing (WGS) for detection of structural chromosomal rearrangements in primary samples of varying DNA quality from 12 patients diagnosed with ALL. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements, aneuploidy assessment and gene deletions. Additional RNA-sequencing and copy number aberrations (CNA) data from Illumina Infinium arrays were also generated and assessed against the linked-read WGS data. RNA-sequencing data was used to support structural chromosomal rearrangements detected in the linked-read WGS data by detecting expressed fusion genes as a consequence of the rearrangements. Illumina Infinium arrays (450k array and/or SNP array) were used to assess CNA status to further support the findings in the linked-read WGS data. The processed CNA data from the primary ALL patient samples has been deposited to GEO. RNA-sequencing, linked-read WGS data, and raw SNP array data from the primary ALL patient samples will not be deposited because the patient/parent consent does not cover depositing data that may be used for large-scale determination of germline variants in a repository. The ALL samples were collected 10-20 years ago from pediatric patients aged 2-15 years, some whom have deceased. The linked-read WGS data and the RNA-sequencing data sets generated in the study are available upon reasonable request from the corresponding author Jessica.Nordlund@medsci.uu.se.
2020-03-02 | GSE117692 | GEO
Project description:With a five-year survival rate of 9%, pancreatic ductal adenocarcinoma (PDAC) the deadliest of all cancers. The rapid mortality makes PDAC difficult to research, and inspires a resolve to create reliable, tractable cellular models for preclinical cancer research. PDAC organoids are increasing used to model PDAC as they maintain the differentiation status, molecular and genomic signatures of the original tumour. In this paper, we present novel methodologies and experimental approaches to develop PDAC organoids from PDX tumours, and the simultaneous development of matched primary cell lines. Moreover, we also identify a method of recapitulating primary cell line cultures to organoids (CLOs). We highlight the usefulness of CLOs as PDAC organoid models, as they maintain similar transcriptomic signatures as their matched patient-derived organoids and PDXs. These models provide a manageable, expandable in vitro resource for downstream applications such as high throughput screening, functional genomics, and tumour microenvironment studies.
2020-02-05 | GSE144737 | GEO
Project description:In our study, we aimed to investigate adaptive processes of tumors under treatment and therefore, generated PDAC patient-derived organoids (PDOs) and 2D cell lines before and after chemotherapy. We enrolled a patient with borderline resectable PDAC who received neoadjuvant FOLFIRINOX. Endoscopic fine needle (pre-FFX) and surgical biopsies (post-FFX) were used to generate PDOs and 2D cells. Whole exome sequencing (WES) and RNA sequencing data of the pre-FFX and post-FFX organoids were compared in order to evaluate the genetic landscape and PDAC subtypes. Although transcriptional subtyping classified both PDOs as classical PDAC, gene set enrichment analysis (GSEA) revealed a reduced pathway activation linked to the basal-like phenotype such as KRAS signaling in the post-FFX organoids. WES did not show major differences in the genetic landscape of the tumor pre- and post-FFX induction suggesting a plasticity process rather than a clonal selection during chemotherapy. 2D cells were subjected to an unbiased automated drug screening of 415 compounds to investigate FFX-induced vulnerabilities. Top targets such as MEK inhibitors were validated manually in the 2D cells and organoids and an increased sensitivity was observed in the post-FFX cells. Thus, integrating functional layers into personalized medicine allows to identify chemotherapy-induced vulnerabilities as potent targeted therapy options in PDAC.
2022-03-09 | GSE193389 | GEO
Project description:The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is affected by a tumor microenvironment (TME). In this study, to recapitulate PDAC TME ex vivo, we cocultured patient-derived PDAC cells with mesenchymal and vascular endothelial cells derived from human induced-pluripotent stem cells (hiPSCs) to create a fused pancreatic cancer organoid (FPCO) in air–liquid interface. FPCOs were further induced to resemble two distinct parts of a PDAC tissue. Owing to various types of cancer associated fibroblasts (CAFs) derived from hiPSCs, the TME consisted of abundant extracellular matrix proteins, which likely conferred strong drug resistance to PDAC cells in one type of FPCOs. Because of re-proliferation capacity of PDAC cells after anticancer drug treatment, the other FPCO is the first culture system for investigating PDAC recurrence. Introducing hiPSC technology, we have created, for the first time, the PDAC organoids representing the heterogeneity of PDAC tissue, a potential platform for screening anticancer drugs.
2023-11-13 | GSE243647 | GEO
Project description:The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is affected by a tumor microenvironment (TME). In this study, to recapitulate PDAC TME ex vivo, we cocultured patient-derived PDAC cells with mesenchymal and vascular endothelial cells derived from human induced-pluripotent stem cells (hiPSCs) to create a fused pancreatic cancer organoid (FPCO) in air–liquid interface. FPCOs were further induced to resemble two distinct parts of a PDAC tissue. Owing to various types of cancer associated fibroblasts (CAFs) derived from hiPSCs, the TME consisted of abundant extracellular matrix proteins, which likely conferred strong drug resistance to PDAC cells in one type of FPCOs. Because of re-proliferation capacity of PDAC cells after anticancer drug treatment, the other FPCO is the first culture system for investigating PDAC recurrence. Introducing hiPSC technology, we have created, for the first time, the PDAC organoids representing the heterogeneity of PDAC tissue, a potential platform for screening anticancer drugs.
2023-11-13 | GSE243649 | GEO
Project description:Deubiquitylating enzymes (DUBs) play an essential role in targeted protein degradation and represent an emerging therapeutic paradigm in cancer. However, their therapeutic potential in pancreatic ductal adenocarcinoma (PDAC) has not been explored. Here, we developed a DUB discovery pipeline, combining activity-based proteomics with a loss-of-function genetic screen in patient-derived PDAC organoids and murine genetic models. This approach identified USP25 as a master regulator of PDAC growth and maintenance. Genetic and pharmacological USP25 inhibition resulted in potent growth impairment in PDAC organoids, while normal pancreatic organoids were insensitive, and caused dramatic regression of patient-derived xenografts. Mechanistically, USP25 deubiquitinated and stabilised the HIF-1a transcription factor. PDAC is characterised by a severely hypoxic microenvironment, and USP25 depletion abrogated HIF-1a transcriptional activity and impaired glycolysis, inducing PDAC cell death in the tumor hypoxic core. Thus, the USP25/HIF-1a axis is an essential mechanism of metabolic reprogramming and survival in PDAC, which can be therapeutically exploited.
2022-03-01 | GSE166077 | GEO