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The 5-Hydroxymethyl...
The 5-Hydroxymethylcytosine Landscape of Prostate Cancer
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- 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
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- 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
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- Feng, F.Y. (author)
- University of California, San Francisco
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(creator_code:org_t)
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et al
- 2022
- 2022
- English 15 s.
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In: Cancer Research. - 0008-5472. ; 82:21, s. 3888-3902
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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
Publication and Content Type
- art (subject category)
- ref (subject category)
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