DNA methylation landscapes in advanced prostate cancer

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, w...

Descripción completa

Detalles Bibliográficos
Autores principales: 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, Perry, Marc, Dang, Ha X., Yang, Rendong, Moussavi-Baygi, Ruhollah, Zhang, Li, Alshalalfa, Mohammed, Chang, S. Laura, 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, Kim, M. Yvonne, 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, Lara, Primo N., Evans, Christopher P., Febbo, Phillip, Batzoglou, Serafim, Knudsen, Karen E., He, Housheng H., Huang, Jiaoti, Zwart, Wilbert, Costello, Joseph F., Luo, Jianhua, Tomlins, Scott A., Wyatt, Alexander W., Dehm, Scott M., Ashworth, Alan, Gilbert, Luke A., Boutros, Paul C., Farh, Kyle, Chinnaiyan, Arul M., Maher, Christopher A., Small, Eric J., Quigley, David A., Feng, Felix Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454228/
https://www.ncbi.nlm.nih.gov/pubmed/32661416
http://dx.doi.org/10.1038/s41588-020-0648-8
Descripción
Sumario: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 only detectable with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hyper-methylation 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 and provides a comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer.

Ejemplares similares