DNA methylation alterations in prostate cancer patient derived xenograft models revealed by whole genome bisulfite sequencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE227086 | GEO | 2023/12/31
REPOSITORIES: GEO
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Project description:DNA methylation alterations are a universal feature of cancer. In prostate cancer, site specific DNA methylation changes have been suggested as driver in disease initial and progression. Here we provide a comprehensive assessment of DNA methylation changes in prostate cancer patient derived xenograft (PDX) models. We delineate patterns of both site specific and global methylation changes and nominate novel candidates for biomarker development. Genome wide DNA methylation profiling of prostate cancer patient derived xenograft and cell line models using Infinium EPIC arrays
2023-12-31 | GSE227695 | GEO
Project description:DNA methylation alterations are a universal feature of cancer. In prostate cancer, site specific DNA methylation changes have been suggested as driver in disease initial and progression. Here we provide a comprehensive assessment of DNA methylation changes in prostate cancer patient derived xenograft (PDX) models. We delineate patterns of both site specific and global methylation changes and nominate novel candidates for biomarker development. Genome wide DNA methylation profiling of prostate cancer patient derived xenograft and cell line models using Infinium EPIC arrays
2023-12-31 | GSE227814 | GEO
Project description:Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period and implanted subcutaneously and under the renal capsule in immuno-deficient mice. To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression. RNA sequencing of prostate cancer tumor tissue and derived xenograft using Illumina HiSeq 2000.
2015-06-30 | E-GEOD-70380 | biostudies-arrayexpress
Project description:Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period and implanted subcutaneously and under the renal capsule in immuno-deficient mice. To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression.
2015-06-30 | GSE70380 | GEO
Project description:DNA methylation and prostate cancer
| PRJNA578778 | ENA
Project description:DNA methylation and prostate cancer
| PRJNA578779 | ENA
Project description:Differential hyper- and hypo-methylation regions in G0 versus G4/G5 CMP The goal of this study is to evaluate changes in CpG methylation profilings of telomere dysfunctional common myeloid progenitor cells (CMP) as compared to their wild type controls Genomic DNA was extracted from sorted CMP populations isolated from 3 pools of G0 or 2 pools of G5 mice using UltraPure Phenol:Chloroform:Isoamyl Alcohol according to manufacturer’s instructions (Life Technologies). 14,000 to 30,000 cells were available for each sample, resulting in a minimum of 45ng of DNA. Genome-wide DNA methylation profiling was performed by RRBS. Library preparation and sequencing were performed at the UT MD Anderson Cancer Center’s DNA Methylation Analysis Core and Sequencing and Microarray Facility, according to published protocols. RRBS sequencing data were aligned and methylation was called using Bismark v0.7.119. In brief, bisulphite-treated DNA was aligned to UCSC Genome Browser mm10 reference genome using Bowtie. In total 29-38 million reads were generated per sample with alignment rates around 63%. Next, MethylKit10 implemented with Fisher’s exact test was used to compare the cytosine methylation profiles of G0 and G5 CMP. Gene promoter regions were calculated based on RefSeq gene annotations with regions starting 1 kb upstream of the annotated transcription start site (TSS) and extending 500 base pairs downstream of TSS. Exons, introns, and CpG islands coordinates were collected from the UCSC Genome Browser mm10 version.
2015-04-09 | E-GEOD-62392 | biostudies-arrayexpress
Project description:Treatment-emergent neuroendocrine prostate cancer (t-NEPC) is a lethal subtype of advanced prostate cancer that develops via NE transdifferentiation of prostate adenocarcinomas in response to androgen receptor (AR)-inhibition therapy. Study of t-NEPC has been hampered by a lack of clinically relevant models. We previously established a unique and first-in-field patient-derived xenograft (PDX) model of adenocarcinoma (LTL331)-to-NEPC (LTL331R) transdifferentiation. In this study, we applied conditional reprogramming (CR) culture to establish a LTL331 PDX-derived cancer cell line named LTL331_CR_Cell. LTL331_CR_Cells retain the same genomic mutations as the LTL331 parental tumor, can be continuously propagated in vitro, and can be genetically manipulated. Androgen deprivation treatment on LTL331_CR_Cells showed no effect on cell proliferation. Transcriptomic analyses comparing the LTL331_CR_Cell to its parental tumor revealed a profound downregulation of the androgen response pathway and an upregulation of stem and basal cell marker genes. The transcriptome of LTL331_CR_Cells partially resembles that of post-castrated LTL331 xenografts in mice. Notably, when grafted under the renal capsule of male NOD/SCID mice, LTL331_CR_Cells spontaneously give rise to NEPC tumors as manifested by the histological expression of the NE marker CD56 and the loss of adenocarcinoma markers such as PSA. Transcriptomic analyses of the newly developed NEPC tumors further demonstrate marked enrichment of NEPC signature genes and loss of AR signaling genes. This study provides a novel research tool based on a unique PDX model. It allows for the investigation of mechanisms underlying t-NEPC development by enabling gene manipulation ex vivo and subsequent functional evaluation in vivo.
2020-06-19 | GSE149091 | GEO
Project description:In order to identify methylation changes in prostate cancer, we performed a genome-wide analysis of DNA methylation using Agilent human CpG island arrays. We then chose specific genes to validate methylation both in the same cases as were hybridized to the array (using quantitative EpiTYPER analysis) and in an independent series of prostate cancer samples (using MethyLight quantitative methylation specific PCR). We specifically chose low grade (Gleason score 6 cases) and high grade (Gleason score 8 cases) to discover methylated genes/loci that may be involved in the progression to a higher grade of prostate cancer. We collected 20 specimens consisting of 10 Gleason 6 and 10 Gleason 8 prostate cancers, and compared these to a reference lymphocyte pool (6 age matched, healthy men) to determine cancer associated methylation changes as well as disease progression associated methylation changes. We performed the differential methylation hybridization procedure as described by Yan et al. (Methods, 2002) on each case to enrich for methylated DNA. Each specimen in the reference pool underwent the same enrichment with amplicons being pooled at the end of the procedure. Each prostate cancer case was subsequently co-hybridized to the microarray with the reference pool.
2009-03-26 | E-GEOD-15298 | biostudies-arrayexpress
Project description:Beginning with precursor lesions, aberrant DNA methylation marks the entire spectrum of prostate cancer progression. We mapped the global DNA methylation patterns in prostate tissues (n=17) and cells (n=2) from fifty nanograms of genomic DNA using Methylplex-Next Generation Sequencing (M-NGS). A Hidden Markov Model (HMM)-based algorithm previously used for Chip-Seq data analysis(http://www.sph.umich.edu/csg/qin/HPeak) was used to locate peaks from mapped reads obtained in each sequencing run. The total methylation events in intergenic/intronic regions between benign adjacent and cancer tissues were comparable. While approximately 20% of all CpG islands (CGIs) (68,508) were methylated in tissues, promoter CGI methylation gradually increased from ~12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues. We found distinct patterns in promoter methylation around transcription start sites, where methylation occurred directly on the CGIs, flanking regions and on CGI sparse promoters. Among the 6,691 methylated promoters in prostate tissues, 2481 differentially methylated regions (DMRs) are cancer specific and several previously studied targets were among them. A novel cancer specific DMR in WFDC2 promoter showed 77% methylation in cancer (17/22), 100% methylation in transformed prostate cell lines (6/6), none in the benign tissues (0/10) and normal PrEC cells. Integration of LNCaP DNA methylation and H3K4me3 data suggested a role for DNA methylation in alternate transcription start site utilization. While methylated promoters containing CGIs had mutually exclusive H3K4me3 modification, the histone mark was absent in CGI sparse promoters. Finally, we observed difference in methylation of LINE-1 elements between transcription factor ERG positive and negative cancers. The comprehensive methylome map presented here will further our understanding of epigenetic regulation of the prostate cancer genome. We mapped the global DNA methylation patterns in prostate tissues (n=17; data not available in GEO - being deposited in dbGaP for controlled access) and cells (n=2) from fifty nanograms of genomic DNA using Methylplex-Next Generation Sequencing (M-NGS). For replicate analysis in cell lines, a total of 4 runs were completed for PrEC prostate normal cell line, and 5 runs were completed for LNCaP prostate cancer cell line. For tissue samples, 2 benign prostate samples were ran twice on illumina next generation sequencing platform to access overall repeatability of M-NGS.
2011-05-09 | E-GEOD-27618 | biostudies-arrayexpress