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The 5-Hydroxymethylcytosine Landscape of Prostate Cancer

Sjostrom, M. (author)
Lund University,Lunds universitet,Bröstcancer Proteogenomik,Forskargrupper vid Lunds universitet,Individuell Bröstcancerbehandling,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröstcancerbehandling,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breast cancer Proteogenomics,Lund University Research Groups,Personalized Breast Cancer Treatment,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast cancer treatment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,University of California, San Francisco
Bjartell, A. (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Urologisk cancerforskning, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Urological cancer, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital
Feng, F.Y. (author)
University of California, San Francisco
 (creator_code:org_t)
et al 
2022
2022
English 15 s.
In: Cancer Research. - 0008-5472. ; 82:21, s. 3888-3902
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating wholegenome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cellfree DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease. Significance: In prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880. © 2022 The Authors.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

5 hydroxymethylcytosine
DNA
transcriptome
5 methylcytosine
5-hydroxymethylcytosine
Article
cancer cell
cancer growth
cancer tissue
cell dedifferentiation
cell proliferation
controlled study
disease course
DNA methylation
genome
human
human tissue
major clinical study
male
metastatic castration resistant prostate cancer
prognosis
sequence analysis
transcriptomics
whole genome bisulfite sequencing
biopsy
prostate
prostate tumor
5-Methylcytosine
Biopsy
Humans
Male
Prostate
Prostatic Neoplasms

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art (subject category)
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By the author/editor
Sjostrom, M.
Bjartell, A.
Feng, F.Y.
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MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Clinical Medicin ...
and Cancer and Oncol ...
Articles in the publication
Cancer Research
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Lund University

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