Epigenetic and transcriptional analysis reveals a core transcriptional program conserved in clonal prostate cancer metastases
| Autor: | Srinivasan Yegnasubramanian, Jonathan W. Simons, William G. Nelson, Michael C. Haffner, Andries M. Bergman, Lodewyk F. A. Wessels, Tesa M. Severson, Matthew L. Freedman, Wilbert Zwart, Tracy Jones, Yanyun Zhu, Angelo M. De Marzo |
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| Přispěvatelé: | Chemical Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Cancer Research Biology SDG 3 – Goede gezondheid en welzijn Metastasis Epigenesis Genetic Histones 03 medical and health sciences Prostate cancer transcriptomics 0302 clinical medicine SDG 3 - Good Health and Well-being Prostate Cell Line Tumor Genetics medicine Transcriptional regulation Humans metastasis Epigenetics Research Articles RC254-282 Epigenomics Prostatic Neoplasms Neoplasms. Tumors. Oncology. Including cancer and carcinogens General Medicine medicine.disease cistrome prostate cancer Gene Expression Regulation Neoplastic ChIP-seq ChIP‐seq 030104 developmental biology medicine.anatomical_structure Oncology Cistrome Receptors Androgen 030220 oncology & carcinogenesis epigenomics Cancer research Molecular Medicine FOXA1 Research Article |
| Zdroj: | Molecular Oncology, Vol 15, Iss 7, Pp 1942-1955 (2021) Molecular Oncology Molecular Oncology, 15(7), 1942-1955. Elsevier |
| ISSN: | 1574-7891 1878-0261 |
| Popis: | The epigenomic regulation of transcriptional programs in metastatic prostate cancer is poorly understood. We studied the epigenomic landscape of prostate cancer drivers using transcriptional profiling and ChIP‐seq in four clonal metastatic tumors derived from a single prostate cancer patient. Our epigenomic analyses focused on androgen receptor (AR), which is a key oncogenic driver in prostate cancer, the AR pioneer factor FOXA1, chromatin insulator CCCTC‐Binding Factor, as well as for modified histones H3K27ac and H3K27me3. The vast majority of AR binding sites were shared among healthy prostate, primary prostate cancer, and metastatic tumor samples, signifying core AR‐driven transcriptional regulation within the prostate cell lineage. Genes associated with core AR‐binding events were significantly enriched for essential genes in prostate cancer cell proliferation. Remarkably, the metastasis‐specific active AR binding sites showed no differential transcriptional output, indicating a robust transcriptional program across metastatic samples. Combined, our data reveal a core transcriptional program in clonal metastatic prostate cancer, despite epigenomic differences in the AR cistrome. Epigenomic and transcriptomic profiling of 4 clonal metastatic samples taken from a patient with prostate cancer during a single autopsy reveals sample‐shared/specific Androgen Receptor (AR) binding sites with enhancer activity. Sample‐shared AR sites are conserved across disease transition states, which are enriched in genes essential for prostate cancer proliferation. Remarkably, genes associated with active metastatic sample‐specific AR binding sites showed no differential transcriptional output. |
| Databáze: | OpenAIRE |
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