Your browser doesn't support javascript.
loading
The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.
Sjöström, Martin; Zhao, Shuang G; Levy, Samuel; Zhang, Meng; Ning, Yuhong; Shrestha, Raunak; Lundberg, Arian; Herberts, Cameron; Foye, Adam; Aggarwal, Rahul; Hua, Junjie T; Li, Haolong; Bergamaschi, Anna; Maurice-Dror, Corinne; Maheshwari, Ashutosh; Chen, Sujun; Ng, Sarah W S; Ye, Wenbin; Petricca, Jessica; Fraser, Michael; Chesner, Lisa; Perry, Marc D; Moreno-Rodriguez, Thaidy; Chen, William S; Alumkal, Joshi J; Chou, Jonathan; Morgans, Alicia K; Beer, Tomasz M; Thomas, George V; Gleave, Martin; Lloyd, Paul; Phillips, Tierney; McCarthy, Erin; Haffner, Michael C; Zoubeidi, Amina; Annala, Matti; Reiter, Robert E; Rettig, Matthew B; Witte, Owen N; Fong, Lawrence; Bose, Rohit; Huang, Franklin W; Luo, Jianhua; Bjartell, Anders; Lang, Joshua M; Mahajan, Nupam P; Lara, Primo N; Evans, Christopher P; Tran, Phuoc T; Posadas, Edwin M.
Afiliação
  • Sjöström M; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Zhao SG; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Levy S; Division of Oncology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Lund, Sweden.
  • Zhang M; Department of Human Oncology, University of Wisconsin-Madison, Madison, WI.
  • Ning Y; William S. Middleton Memorial Veterans' Hospital, Madison, WI.
  • Shrestha R; Bluestar Genomics Inc., San Diego, CA.
  • Lundberg A; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Herberts C; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Foye A; Bluestar Genomics Inc., San Diego, CA.
  • Aggarwal R; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Hua JT; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Li H; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Bergamaschi A; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Maurice-Dror C; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Maheshwari A; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Chen S; Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.
  • Ng SWS; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Ye W; Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.
  • Petricca J; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Fraser M; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Chesner L; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Perry MD; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Moreno-Rodriguez T; Bluestar Genomics Inc., San Diego, CA.
  • Chen WS; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Alumkal JJ; BC Cancer, Vancouver, BC, Canada.
  • Chou J; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Morgans AK; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Beer TM; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Thomas GV; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Gleave M; Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
  • Lloyd P; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Phillips T; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • McCarthy E; Department of Automation, Xiamen University, Xiamen, Fujian, China.
  • Haffner MC; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
  • Zoubeidi A; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Annala M; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Reiter RE; Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
  • Rettig MB; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Witte ON; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Fong L; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Bose R; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Huang FW; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Luo J; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Bjartell A; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Lang JM; Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA.
  • Mahajan NP; Division of Hematology and Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI.
  • Lara PN; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
  • Evans CP; Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA.
  • Tran PT; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
  • Posadas EM; Knight Cancer Institute, Oregon Health and Science University, Portland, OR.
Cancer Res ; 82(21): 3888-3902, 2022 11 02.
Article em En | MEDLINE | ID: mdl-36251389
ABSTRACT
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 whole-genome 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 cell-free 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.
Assuntos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / 5-Metilcitosina Tipo de estudo: Prognostic_studies Limite: Humans / Male Idioma: En Revista: Cancer Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Canadá
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / 5-Metilcitosina Tipo de estudo: Prognostic_studies Limite: Humans / Male Idioma: En Revista: Cancer Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Canadá