ID
45496
Descrição
Principal Investigator: Dr. Arul M. Chinnaiyan, MD,PhD, University of Michigan, Ann Arbor, MI, USA MeSH: Prostatic Neoplasms https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000597 Aberrant DNA methylation changes are known to occur during prostate cancer progression beginning with precursor lesions. Utilizing fifty nanograms of genomic DNA in Methylplex-Next Generation Sequencing (M-NGS) we mapped the global DNA methylation patterns in prostate tissues (n=17) and cells (n=2). Peaks were located from mapped reads obtained in each sequencing run using a Hidden Markov Model (HMM)-based algorithm previously used for Chip-Seq data analysis(http://www.sph.umich.edu/csg/qin/HPeak). The total methylation events in intergenic/intronic regions between benign adjacent and cancer tissues were comparable. Promoter CGI methylation gradually increased from -12.6% in benign samples to 19.3% and 21.8% in localized and metastatic cancer tissues and approximately 20% of all CpG islands (CGIs) (68,508) were methylated in tissues. We observed 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. Overall Design: 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). 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 sequenced twice on Illumina next generation sequencing platform to access overall repeatability of M-NGS.
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Versões (2)
- 14/11/2022 14/11/2022 - Dr. med. Lucy Kessler
- 13/12/2022 13/12/2022 - Kristina Keller
Titular dos direitos
Dr. Arul M. Chinnaiyan, MD,PhD, University of Michigan, Ann Arbor, MI, USA
Transferido a
13 de dezembro de 2022
DOI
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Licença
Creative Commons BY 4.0
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dbGaP phs000597 DNA Methylation Analysis of Prostate Cancer
Eligibility Criteria
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, subject source, subject ID, and affection status of participants with or without prostate cancer and involved in the "DNA Methylation Analysis of Prostate Cancer Cell Lines and Tissues Using Next Generation Sequencing" project.
- Subject ID, sample ID, and sample use of samples obtained of participants with or without prostate cancer and involved in the "DNA Methylation Analysis of Prostate Cancer Cell Lines and Tissues Using Next Generation Sequencing" project.
- Subject ID, age, sex, race, gene fusion status in ETS family of participants with or without prostate cancer and involved in the "DNA Methylation Analysis of Prostate Cancer Cell Lines and Tissues Using Next Generation Sequencing" project.
- Sample ID, body site where sample was obtained, analyte type, histological type of sample, sample information if it obtained from primary tumor, metastasis, or transformed cell line, primary tumor location, primary and secondary Gleason, Gleason score of participants with or without prostate cancer and involved in the "DNA Methylation Analysis of Prostate Cancer Cell Lines and Tissues Using Next Generation Sequencing" project.
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Eligibility Criteria
- StudyEvent: SEV1
- Eligibility Criteria
- Subject ID, consent group, subject source, subject ID, and affection status of participants with or without prostate cancer and involved in the "DNA Methylation Analysis of Prostate Cancer Cell Lines and Tissues Using Next Generation Sequencing" project.
- Subject ID, sample ID, and sample use of samples obtained of participants with or without prostate cancer and involved in the "DNA Methylation Analysis of Prostate Cancer Cell Lines and Tissues Using Next Generation Sequencing" project.
- Subject ID, age, sex, race, gene fusion status in ETS family of participants with or without prostate cancer and involved in the "DNA Methylation Analysis of Prostate Cancer Cell Lines and Tissues Using Next Generation Sequencing" project.
- Sample ID, body site where sample was obtained, analyte type, histological type of sample, sample information if it obtained from primary tumor, metastasis, or transformed cell line, primary tumor location, primary and secondary Gleason, Gleason score of participants with or without prostate cancer and involved in the "DNA Methylation Analysis of Prostate Cancer Cell Lines and Tissues Using Next Generation Sequencing" project.
C0680251 (UMLS CUI [1,2])
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