Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA391448 | ENA |
REPOSITORIES: ENA
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Project description:A biobank of 30 molecularly characterized patient-derived xeongraft models of pediatric brain tumors
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Project description:A biobank of 30 molecularly characterized patient-derived xeongraft models of pediatric brain tumors [Illumina HumanMethylation]
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Project description:Pediatric rhabdoid tumors of kidney and brain show many differences in gene expression but share dysregulation of cell cycle and epigenetic effector genes
2025-01-24 | E-GEOD-35493 | ExpressionAtlas
Project description:Osteosarcoma (OS) and Ewing’s sarcoma (EW) are the two most common pediatric solid tumors, after brain tumors. Multimodal treatments have significantly improved prognosis in localized disease but outcome is still poor in metastatic patients, for whom therapeutic options are often inadequate. Preclinical drug testing to identify promising treatment options that match the molecular make-up of these tumors is hampered by the lack of appropriate and molecularly well-characterized patient-derived models. To address this need, a panel of patient-derived xenografts (PDX) was established by subcutaneous implantation of fresh, surgically resected OS and EW tumors in NSG mice. Tumors were re-transplanted to next mice generations and fragments were collected for histopathological and molecular characterization. A model was considered established after observing stable histological and molecular features for at least three passages. To evaluate the similarity of the model with primary tumor, we performed a global gene expression profiling and tissue microarrays (TMA), to assess tumor specific biomarkers on tissues from OS/EW tumors and their PDXs (1st and 3rd passage). Moreover, we verified the feasibility of these models for preclinical drug testing. We implanted 61 OS and 29 EW samples: 14/38 (37%) primary OS and 9/23 (39%) OS lung metastases successfully engrafted; while among EW, 5/26 (19%) primary samples and 1/3 (33%) metastases were established. Comparison between patient samples and PDXs, highlighted that histology and genetic characteristics of PDXs were stable and maintained over passages. In particular, correlative analysis between OS and EW samples and their PDXs was extremely high (Pearson’s r range r=0.94-0.96), while patient-derived primary cultures displayed reduced correlation with human samples (r=0.90-0.93), indicating that in vitro adaptation superimpose molecular alterations that create genetic diversion from original tumors. No significant differentially expressed gene profile was observed from the comparison between EW samples and PDXs (fold change > 2, adjusted p <0.05 at paired t-test). In OS, the comparison between OS patient-derived tumors and PDX indicated differences in 397 genes, mostly belonging to immune system functional category. This is in line with the idea that human immune cells are gradually replaced by murine counterparts upon engraftment in the mouse. As proof-of concept, two EW PDX and one OS PDX have been treated with conventional and innovated drugs to test their value in terms of drug-sensitivity prediction. Overall, our study indicated that PDX models maintained the histological and genetic markers of the tumor samples and represent reliable models to test sensitivity to novel drug associations.
2019-08-27 | E-MTAB-7568 | biostudies-arrayexpress
Project description:Expression data from human brain tumors and human normal brain
2025-01-24 | E-GEOD-50161 | ExpressionAtlas
Project description:Gene expression profile of pediatric and adult brain tumor types and normal brain
2025-01-24 | E-GEOD-66354 | ExpressionAtlas
Project description:Brain tumors are the leading cause of cancer-related death in children. Genomic studies have provided insights into molecular
subgroups and oncogenic drivers of pediatric brain tumors that may lead to novel therapeutic strategies. To evaluate new
treatments, better preclinical models adequately reflecting the biological heterogeneity are needed. Through the Children’s Oncology Group ACNS02B3 study, we have generated and comprehensively characterized 30 patient-derived orthotopic
xenograft models and 7 cell lines representing 14 molecular subgroups of pediatric brain tumors. Patient-derived orthotopic
xenograft models were found to be representative of the human tumors they were derived from in terms of histology, immunohistochemistry, gene expression, DNA methylation, copy number, and mutational profiles. In vivo drug sensitivity of targeted therapeutics was associated with distinct molecular tumor subgroups and specific genetic alterations. These models and their molecular characterization provide an unprecedented resource for the cancer community to study key oncogenic drivers and to evaluate novel treatment strategies.
| EGAS00001002536 | EGA
Project description:Sixteen pre-treatment samples of pathologically confirmed solitary fibrous tumors (SFT) were available for RNA profiling. They were collected from 16 patients who underwent initial surgery and/or diagnostic biopsy. Samples were macrodissected by pathologists, and frozen within 30 min of removal in liquid nitrogen in our biobank (Biobank authorization number 2008/70, APHM). All profiled specimens contained more than 70% tumor cells. Each patient gave written informed consent for molecular analysis, and the study was approved by our institutional ethics committee. Total RNA was extracted from frozen samples by using the All-In-One Norgen Biotek kit (Thorold, Canada) and integrity was controlled by Agilent analysis (Bioanalyzer, Palo Alto, CA). Gene expression profiling was done with Affymetrix U133 Plus 2.0 human oligonucleotide microarrays with labeling kit and protocol from manufacturer.
2013-11-12 | E-MTAB-1361 | biostudies-arrayexpress
Project description:Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancer are limited and hard to establish. We present a protocol that enables efficient generation, expansion and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.
2023-12-01 | GSE247380 | GEO
Project description:Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancer are limited and hard to establish. We present a protocol that enables efficient generation, expansion and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.
2023-12-01 | GSE247231 | GEO