Scholars@Duke

The DNA methylation landscape of advanced prostate cancer.

Publication ,  Journal Article
Zhao, SG; Chen, WS; Li, H; Foye, A; Zhang, M; Sjöström, M; Aggarwal, R; Playdle, D; Liao, A; Alumkal, JJ; Das, R; Chou, J; Hua, JT; Chow, ED ...
Published in: Nat Genet
August 2020
Published version (DOI) Link to item

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.

Duke Scholars

Jiaoti Huang
Author Jiaoti Huang Pathology
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Published In

Nat Genet

DOI

10.1038/s41588-020-0648-8

EISSN

1546-1718

Publication Date

August 2020

Volume

52

Issue

8

Start / End Page

778 / 789

Location

United States

Related Subject Headings

  • Whole Genome Sequencing
  • Sequence Analysis, DNA
  • Prostatic Neoplasms
  • Prospective Studies
  • Mutation
  • Middle Aged
  • Male
  • Humans
  • Genome
  • Gene Expression Regulation, Neoplastic
 

Citation

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ICMJE
MLA
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Zhao, S. G., Chen, W. S., Li, H., Foye, A., Zhang, M., Sjöström, M., … Feng, F. Y. (2020). The DNA methylation landscape of advanced prostate cancer. Nat Genet, 52(8), 778–789. https://doi.org/10.1038/s41588-020-0648-8
Zhao, Shuang G., William S. Chen, Haolong Li, Adam Foye, Meng Zhang, Martin Sjöström, Rahul Aggarwal, et al. “The DNA methylation landscape of advanced prostate cancer.” Nat Genet 52, no. 8 (August 2020): 778–89. https://doi.org/10.1038/s41588-020-0648-8.
Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjöström M, et al. The DNA methylation landscape of advanced prostate cancer. Nat Genet. 2020 Aug;52(8):778–89.
Zhao, Shuang G., et al. “The DNA methylation landscape of advanced prostate cancer.” Nat Genet, vol. 52, no. 8, Aug. 2020, pp. 778–89. Pubmed, doi:10.1038/s41588-020-0648-8.
Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjöström M, Aggarwal R, Playdle D, Liao A, Alumkal JJ, Das R, Chou J, Hua JT, Barnard TJ, Bailey AM, Chow ED, Perry MD, Dang HX, Yang R, Moussavi-Baygi R, Zhang L, Alshalalfa M, Laura Chang S, Houlahan KE, Shiah Y-J, Beer TM, Thomas G, Chi KN, Gleave M, Zoubeidi A, Reiter RE, Rettig MB, Witte O, Yvonne Kim M, Fong L, Spratt DE, Morgan TM, Bose R, Huang FW, Chesner L, Shenoy T, Goodarzi H, Asangani IA, Sandhu S, Lang JM, Mahajan NP, Lara PN, Evans CP, Febbo P, Batzoglou S, Knudsen KE, He HH, Huang J, Zwart W, Costello JF, Luo J, Tomlins SA, Wyatt AW, Dehm SM, Ashworth A, Gilbert LA, Boutros PC, Farh K, Chinnaiyan AM, Maher CA, Small EJ, Quigley DA, Feng FY. The DNA methylation landscape of advanced prostate cancer. Nat Genet. 2020 Aug;52(8):778–789.

Published In

Nat Genet

DOI

10.1038/s41588-020-0648-8

EISSN

1546-1718

Publication Date

August 2020

Volume

52

Issue

8

Start / End Page

778 / 789

Location

United States

Related Subject Headings

  • Whole Genome Sequencing
  • Sequence Analysis, DNA
  • Prostatic Neoplasms
  • Prospective Studies
  • Mutation
  • Middle Aged
  • Male
  • Humans
  • Genome
  • Gene Expression Regulation, Neoplastic