Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA238250 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer
| PRJEB6530 | ENA
Project description:Androgen receptor (AR) drives prostate cancer (PCa) development and progression. AR chromatin binding profiles are highly plastic and form recurrent programmatic changes that differentiate disease stages, subtypes and patient outcomes. While prior studies focused on concordance between patient subgroups, inter-tumor heterogeneity of AR enhancer selectivity remains unexplored. Here we report high levels of AR chromatin binding heterogeneity in human primary prostate tumors, that unexpectedly strongly overlap with heterogeneity observed in healthy prostate epithelium. Such heterogeneity has functional consequences, as somatic mutations converge on commonly-shared AR sites in primary over metastatic tissues. In contrast, less-frequently shared AR sites associate strongly with AR-driven gene expression, while such heterogeneous AR enhancer usage also distinguishes patients’ outcome. These findings indicate that epigenetic heterogeneity in primary disease is directly informative for risk of biochemical relapse. Cumulatively, our results illustrate an extraordinary level of AR enhancer heterogeneity in primary PCa driving differential expression and clinical impact.
2022-11-12 | GSE217319 | GEO
Project description:Tumor Cell Heterogeneity and Dormancy in Single Disseminated Prostate Cancer Cells
| PRJNA212632 | ENA
Project description:Estrogen Receptor alpha (ERa) is the main driver of luminal breast cancer development and progression, and represents the main drug target in patient care. ERa chromatin binding has been extensively studied in breast cancer cell lines and a number of human tumors, often focused on differential binding patterns between groups or conditions. However, little is known about the inter-tumor heterogeneity of ERa chromatin action. Here, we use a large set of ERa ChIP-seq data from 70 ERa+ breast cancers (40 women & 30 men) to explore general inter-patient heterogeneity in ERa DNA binding in breast cancers. We found a total universe of 84,565 and 101,653 ERa sites in females and males respectively, with merely 1.2% and 5% of sites shared in at least half of the tumors analyzed, reflecting a high level of inter-patient heterogeneity. This heterogeneity was found to be most variable at putative enhancers as opposed to promoter regions, potentially reflecting a level of functional redundancy in enhancer action. Interestingly, commonly shared ERa sites showed the highest estrogen-driven enhancer activity, as determined using a massive parallel reporter assay, and were most-engaged in long-range chromatin interactions. In addition, the most-commonly shared ERa-occupied enhancers were found enriched for breast cancer risk SNP loci. We experimentally illustrate such SNVs can impact chromatin binding potential for ERa and its pioneer factor FOXA1. Finally, in the TCGA breast cancer cohort, we could confirm these variations to associate with differences in expression for the target gene. Cumulatively, our data reveal a natural hierarchy of ERa-chromatin interactions in breast cancers within a highly heterogeneous inter-tumor ERa landscape, with the most-common shared regions being most active and affected by germline functional risk SNPs for breast cancer development.
2024-05-22 | PXD045526 | Pride
Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 21 xenograft tumors
2013-01-12 | E-GEOD-41188 | biostudies-arrayexpress
Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 22 xenograft tumors
2013-01-12 | E-GEOD-41192 | biostudies-arrayexpress
Project description:Prostate cancer research is hampered by a lack of preclinical models which accurately reproduce clinical heterogeneity. We have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from prostate cancer biopsy tissue, and also new lines from metastatic tissue. The lines retained salient features of the original patient tumors, including histopathological and molecular characteristics. Furthermore, they span major subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of neuroendocrine transdifferentiation. This publicly-available resource provides novel tools for the next-generation of prostate cancer research and therapy development.
2013-01-12 | GSE41192 | GEO
Project description:Prostate cancer research is hampered by a lack of preclinical models which accurately reproduce clinical heterogeneity. We have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from prostate cancer biopsy tissue, and also new lines from metastatic tissue. The lines retained salient features of the original patient tumors, including histopathological and molecular characteristics. Furthermore, they span major subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of neuroendocrine transdifferentiation. This publicly-available resource provides novel tools for the next-generation of prostate cancer research and therapy development.
2013-01-12 | GSE41188 | GEO
Project description:Functional Significance of Prostate Cancer risk-SNPs
| PRJNA294705 | ENA