Project description:This study investigates the genomic and transcriptomic characteristics of Wilm's tumour organoids .
This dataset contains all the data available for this study on 2019-09-05.
Project description:OCT-embedded PDAC tissues were assessed for stromal and tumour epithelial regions which were both laser-capture microdissected from 33 patients. Integration of these proteomic profiles with transcriptomic data lead to the identification of two spatially confined tumour microenvironment programs: deserted and reactive.
Project description:The deubiquitinating enzyme BAP1 is a tumour suppressor, amongst others involved in cholangiocarcinoma. BAP1 has many proposed molecular targets, while its Drosophila homolog is known to deubiquitinate Histone H2AK119. Here, we mutate BAP1 by CRISPR/Cas9 in normal human liver organoids. We find that BAP1 controls the expression of junctional/cytoskeleton components by regulating chromatin accessibility. Consequently, we observe loss of multiple epithelial characteristics, while motility increases. Importantly, restoring the catalytic activity of BAP1 in the nucleus rescues these cellular and molecular changes. We engineer human liver organoids to combine four common cholangiocarcinoma mutations (TP53, PTEN, SMAD4, NF1). In this genetic background, BAP1 loss results in acquisition of malignant features upon xenotransplantation. Thus, control of epithelial identity through the regulation of chromatin accessibility appears a key aspect of BAP1’s tumour suppressor function. Organoid technology combined with CRISPR/Cas9 provides an experimental platform for mechanistic studies of cancer gene function in a human context.
Project description:Gene expression microarray profiling on glioblastoma intra-tumour regions, where the study hypothesis states that the infiltrative tumour margin harbours a distinct transcriptomic profile from all non-infiltrative tumour regions. Data is from three patients (patient 9, 14 and 15) where regions 1-4 per patient were obtained from non-infiltrative intra-tumour regions, and region 5 was obtained from the infiltrative margin. All patients underwent craniotomy with intra-operative image guidance and visualization of 5ALA induced fluorescence to obtain infiltrative margin biopsies.
Project description:We show that oncogenesis in Wilms’ tumor - the most common pediatric renal cancer- is mediated by small non-coding RNAs miRNAs.Interestingly, several differentially expressed miRNAs target genes that are known to play important role in kidney development. miRNA profile of Wilm's tumor vs. normal kidney with two color microarray protocol
Project description:We established human colorectal tumor organoids from benign adenoma, primary colorectal cancer or metastasized colorectal cancer. The gene signature of tumor organoids associated with their tumor progression status. We also generated genome-edited organoids from human intestinal organoids recapitulating adenoma-carcinoma sequence. Gene expression signature of the genome engineered organoids were similar to that of adenoma organoids. This result indicated multiple (up to five) genetic mutations were insufficient for gene expression reprogramming of colorectal cancer. We used microarrays to detail the global program of gene expression in human colorectal tumor organoids and artificially mutation introduced organoids. To assess the expression profiling of genome-engineered organoids, we prepared total-RNA from cultured adenoma, carcinoma and genome-engineered organoids. We produced two types of genome-engineered organoids using the CRISPR/Cas9 or lentivirus vector system. Each engineered gene and engineered methods are described as a single alphabet and method name, respectively, in the sample characteristics field. The abbreviations for the engineered genes are as follows. 1) Genome-engineered organoids with CRISPR/Cas9 A = APC deletion; K = KRAS G12V knock in; S = Smad4 deletion; T = TP53 deletion; P = PIK3CA E545K knock in. 2) Genome-engineered organoids with Lent virus vector B = CTNNB1 S33Y overexpression; K = KRAS G12V overexpression; S = Smad4 shRNA overexpression; T = TP53 shRNA overexpression; P = PIK3CA E545K overexpression.
Project description:We report the microRNA profiles of the mouse embryonic stem cell (E14IV), which have been deleted for tumour suppressor Wilms' Tumour 1 (WT1), and induced with retinoic acid. Additionally, cells that had an inducibe WT1 expression where also used to compare the microRNA profile during different time points of WT1 induction.
Project description:Squamocolumnar junction (SCJ) of the uterine cervix is a target of human papilloma virus (HPV) infection and thereby a putative cell-of-origin for uterine cervical cancer. However at present, in vitro models that accurately phenocopy its homeostasis is lacking. In this study, we aimed at establishing organoids of SCJ cells and identifying its characteristics. Samples were collected from the uterine cervix of 4 cases who underwent hysterectomy at our department, and processed to initiate organoid culture. Organoids were obtained from 3 samples among them, and they were analyzed both histologically and by transcriptome analysis.
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.