Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole genome sequencing with histopathological features
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ABSTRACT:
PROVIDER: EGAS00001007438 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:We performed whole genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and regional lymph nodes of five treatment-naive patients with locally advanced disease who underwent radical prostatectomy. Whole genome sequencing was performed as 150bp paired end reads on the Illumina NovaSeq 6000 platform.
| EGAD00001011174 | EGA
Project description:The role of lymph node metastases in distant prostate cancer dissemination and lethality is ill defined. Patients with metastases restricted to lymph nodes have a better prognosis than those with distant metastatic spread, suggesting the possibility of distinct aetiologies. To explore this, we traced patterns of cancer dissemination using tumour phylogenies inferred from genome-wide copy-number profiling of 48 samples across 3 patients with lymph node metastatic disease and 3 patients with osseous metastatic disease. Our results show that metastatic cells in regional lymph nodes originate from evolutionary advanced extra-prostatic tumour cells rather than less advanced central tumour cell populations. In contrast, osseous metastases do not exhibit such a constrained developmental lineage, arising from either intra or extra-prostatic tumour cell populations, at early and late stages in the evolution of the primary. Collectively, this comparison suggests that lymph node metastases may not be an intermediate developmental step for distant osseous metastases, but rather represent a distinct metastatic lineage.
| EGAS00001001801 | EGA
Project description:B cell receptor (BCR)-sequencing from 3 donors with prostate cancer. The sources are Peripheral blood B cells (P), tumour draining lymph nodes (S) and non-draining lymph nodes (N).
2023-01-01 | E-MTAB-11862 | biostudies-arrayexpress
Project description:To investigate the identity of the tissue origin for metastases, we compared gene expression profiles of the prostate tissues and seminal vesicles from PB-Pten-NICD mice and those of 7 lung metastases from different mice. Three respective cell lines established from primary seminal vesicle tumors, primary prostate tumors, and lung metastases in PB-Pten-NICD mice were also included in the microarray analysis. We hypothesized that the gene expression profiles of primary and metastatic tumors should resemble those of their tissue origins. We identified genes differentially expressed between the seminal vesicle and prostate tumors. The expression profiles of the two cell lines established from primary tumors resembled those of their respective tissue origins, which supports our hypothesis. The expression profile of the metastatic cell line resembled those of the prostate tumor tissues, indicating the prostate as its tissue of origin. The expression profiles of 2 metastatic specimens each resembled those of the seminal vesicle tumors and the prostate tumors, respectively, while the expression profiles of the remaining 3 samples displayed a mixed pattern. This study suggests that metastatic tumors in this model may have originated from either the prostate, or the seminal vesicles, or both.
2016-09-09 | GSE72549 | GEO
Project description:BACKGROUND: Prostate cancer is the most frequently diagnosed cancer among men in the United States. In contrast, cancer of the seminal vesicle is exceedingly rare, despite that the prostate and seminal vesicle share similar histology, secretory function, androgen dependency, blood supply, and (in part) embryonic origin. We hypothesized that gene-expression differences between prostate and seminal vesicle might inform mechanisms underlying the higher incidence of prostate cancer. METHODS: Whole-genome DNA microarrays were used to profile gene expression of 11 normal prostate and 7 seminal vesicle specimens (including 6 matched pairs) obtained from radical prostatectomy. Supervised analysis was used to identify genes differentially expressed between normal prostate and seminal vesicle, and this list was then cross-referenced to genes differentially expressed between normal and cancerous prostate. Expression patterns of selected genes were confirmed by immunohistochemistry using a tissue microarray. We identified 32 genes that displayed a highly statistically-significant expression pattern with highest levels in seminal vesicle, lower levels in normal prostate, and lowest levels in prostate cancer. Among these genes was the known candidate prostate tumor suppressor GSTP1 (involved in xenobiotic detoxification). The expression pattern of GSTP1 and four other genes, ABCG2 (xenobiotic transport), CRABP2 (retinoic acid signaling), GATA3 (lineage-specific transcription) and SLPI (immune response), was confirmed by immunohistochemistry. CONCLUSIONS: Our findings identify candidate prostate cancer genes whose reduced expression in prostate (compared to seminal vesicle) may be permissive to prostate cancer initiation. Such genes and their pathways may inform mechanisms of prostate carcinogenesis, and suggest new opportunities for prostate cancer prevention. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: normal prostate vs normal seminal vesicle sample Individual Keywords: Logical Set cDNA microarrays from the Stanford Functional Genomics Facility were used for expression profiling of 11 normal prostate and 7 seminal vesicle specimens (6 of which were matched pairs), against a universal RNA reference. Extracted expression ratios were normalized by array then mean centered by gene, and expression differences between normal prostate and seminal vesicle identified using Significance Analysis of Microarrays (SAM).
2008-05-08 | E-GEOD-11376 | biostudies-arrayexpress
Project description:BACKGROUND: Prostate cancer is the most frequently diagnosed cancer among men in the United States. In contrast, cancer of the seminal vesicle is exceedingly rare, despite that the prostate and seminal vesicle share similar histology, secretory function, androgen dependency, blood supply, and (in part) embryonic origin. We hypothesized that gene-expression differences between prostate and seminal vesicle might inform mechanisms underlying the higher incidence of prostate cancer. METHODS: Whole-genome DNA microarrays were used to profile gene expression of 11 normal prostate and 7 seminal vesicle specimens (including 6 matched pairs) obtained from radical prostatectomy. Supervised analysis was used to identify genes differentially expressed between normal prostate and seminal vesicle, and this list was then cross-referenced to genes differentially expressed between normal and cancerous prostate. Expression patterns of selected genes were confirmed by immunohistochemistry using a tissue microarray. We identified 32 genes that displayed a highly statistically-significant expression pattern with highest levels in seminal vesicle, lower levels in normal prostate, and lowest levels in prostate cancer. Among these genes was the known candidate prostate tumor suppressor GSTP1 (involved in xenobiotic detoxification). The expression pattern of GSTP1 and four other genes, ABCG2 (xenobiotic transport), CRABP2 (retinoic acid signaling), GATA3 (lineage-specific transcription) and SLPI (immune response), was confirmed by immunohistochemistry. CONCLUSIONS: Our findings identify candidate prostate cancer genes whose reduced expression in prostate (compared to seminal vesicle) may be permissive to prostate cancer initiation. Such genes and their pathways may inform mechanisms of prostate carcinogenesis, and suggest new opportunities for prostate cancer prevention. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Disease State: normal prostate vs normal seminal vesicle sample Individual Keywords: Logical Set
2008-05-08 | GSE11376 | GEO
Project description:Small molecules extracted from mouse mesenteric lymph nodes.
| MSV000080181 | GNPS
Project description:Similar to other genotoxic polycyclic aromatic hydrocarbons (PAHs), benzo[a]pyrene (BaP) is known to produce stable DNA adducts and other DNA damage. BaP is a powerful carcinogen and can induce tumors in the accessory sex organs (including prostate) of rodents. In the present study, we have investigated the potential role of BaP as an epimutagen in vivo during chemical carcinogenesis. We have analyzed the DNA methylation profile, genome-wide, of seminal vesicles of Big Blue® mice exposed to chronic doses of BaP over a period of 6 weeks, both immediately after the termination of exposure and several weeks after-treatment in mice that have developed tumors on the accessory sex organs. Mice treated with chronic doses of DMSO (sham) were used as control. We have used a genome-wide microarray-based approach to catalogue the DNA methylation profile in the seminal vesicles of mice injected intraperitoneally with chronic doses of BaP (experimental) or DMSO (control).
2013-06-30 | E-GEOD-41422 | biostudies-arrayexpress
Project description:The lymph of normal rabbit lymph nodes and metastatic lymph nodes of breast cancer were extracted by contrast-enhanced ultrasound for proteomic analysis, and the differential proteins affecting metastasis were obtained.
2023-11-29 | PXD047360 |
Project description:Mechanistic links between development and disease can be exploited to provide clues to the cellular signalling pathways that might become re-activated during adult pathogenesis such as those affecting the prostate. However, the mechanisms underpinning prostate development require further characterisation. Previously, our group developed novel methods to produce prostate organoids using induced pluripotent stem cells (iPSCs). Here, we show that the iPSCs can be fully differentiated into prostate organoids using neonatal rodent seminal vesicle mesenchyme (SVM) in vitro. Additionally, we elucidated molecular drivers of prostate induction through RNA-sequencing analyses of the rat urogenital sinus (the embryonic precursor of the prostate gland) as well as the neonatal seminal vesicles. We identified candidate drivers evident in the inductive mesenchyme and epithelium involved with prostate specification. Our top candidates included Spx, Trib3, Snai1, Snai2, Nrg2, and Lrp4. This work lays the foundations to further interrogate the reactivation of developmental genes in adulthood, leading to prostate disease.
2023-07-05 | GSE234252 | GEO