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The DNA methylation landscape of advanced prostate cancer.
Zhao, Shuang G; Chen, William S; Li, Haolong; Foye, Adam; Zhang, Meng; Sjöström, Martin; Aggarwal, Rahul; Playdle, Denise; Liao, Arnold; Alumkal, Joshi J; Das, Rajdeep; Chou, Jonathan; Hua, Junjie T; Barnard, Travis J; Bailey, Adina M; Chow, Eric D; Perry, Marc D; Dang, Ha X; Yang, Rendong; Moussavi-Baygi, Ruhollah; Zhang, Li; Alshalalfa, Mohammed; Laura Chang, S; Houlahan, Kathleen E; Shiah, Yu-Jia; Beer, Tomasz M; Thomas, George; Chi, Kim N; Gleave, Martin; Zoubeidi, Amina; Reiter, Robert E; Rettig, Matthew B; Witte, Owen; Yvonne Kim, M; Fong, Lawrence; Spratt, Daniel E; Morgan, Todd M; Bose, Rohit; Huang, Franklin W; Li, Hui; Chesner, Lisa; Shenoy, Tanushree; Goodarzi, Hani; Asangani, Irfan A; Sandhu, Shahneen; Lang, Joshua M; Mahajan, Nupam P; Lara, Primo N; Evans, Christopher P; Febbo, Phillip.
Afiliação
  • Zhao SG; Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
  • Chen WS; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
  • Li H; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Foye A; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Zhang M; Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
  • Sjöström M; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Aggarwal R; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Playdle D; Yale School of Medicine, New Haven, CT, USA.
  • Liao A; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Alumkal JJ; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Das R; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Chou J; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Hua JT; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Barnard TJ; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Bailey AM; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Chow ED; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Perry MD; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Dang HX; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Yang R; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Moussavi-Baygi R; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Zhang L; Illumina Inc., San Diego, CA, USA.
  • Alshalalfa M; Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
  • Laura Chang S; Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR, USA.
  • Houlahan KE; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Shiah YJ; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Beer TM; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Thomas G; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Chi KN; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Gleave M; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
  • Zoubeidi A; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Reiter RE; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Rettig MB; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Witte O; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Yvonne Kim M; Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.
  • Fong L; Center for Advanced Technology, University of California San Francisco, San Francisco, CA, USA.
  • Spratt DE; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Morgan TM; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Bose R; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Huang FW; McDonnell Genome Institute, Washington University, St. Louis, MO, USA.
  • Li H; Department of Internal Medicine, Washington University, St. Louis, MO, USA.
  • Chesner L; Siteman Cancer Center, Washington University, St. Louis, MO, USA.
  • Shenoy T; The Hormel Institute, University of Minnesota, Austin, MN, USA.
  • Goodarzi H; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Asangani IA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Sandhu S; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • Lang JM; Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Mahajan NP; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Lara PN; Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
  • Evans CP; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
  • Febbo P; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Nat Genet ; 52(8): 778-789, 2020 08.
Article em En | MEDLINE | ID: mdl-32661416
ABSTRACT
Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF. We also identified intergenic regions where methylation is associated with RNA expression of the oncogenic driver genes AR, MYC and ERG. Finally, we showed that differential methylation during progression preferentially occurs at somatic mutational hotspots and putative regulatory regions. This study is a large integrated study of whole-genome, whole-methylome and whole-transcriptome sequencing in metastatic cancer that provides a comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Metilação de DNA Tipo de estudo: Clinical_trials / Observational_studies / Risk_factors_studies Limite: Aged / Aged80 / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Metilação de DNA Tipo de estudo: Clinical_trials / Observational_studies / Risk_factors_studies Limite: Aged / Aged80 / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article