The Proteogenomic Landscape of Curable Prostate Cancer

Publication date: 18 March 2019Source: Cancer Cell, Volume 35, Issue 3Author(s): Ankit Sinha, Vincent Huang, Julie Livingstone, Jenny Wang, Natalie S. Fox, Natalie Kurganovs, Vladimir Ignatchenko, Katharina Fritsch, Nilgun Donmez, Lawrence E. Heisler, Yu-Jia Shiah, Cindy Q. Yao, Javier A. Alfaro, Stas Volik, Anna Lapuk, Michael Fraser, Ken Kron, Alex Murison, Mathieu Lupien, Cenk SahinalpSummaryDNA sequencing has identified recurrent mutations that drive the aggressiveness of prostate cancers. Surprisingly, the influence of genomic, epigenomic, and transcriptomic dysregulation on the tumor proteome remains poorly understood. We profiled the genomes, epigenomes, transcriptomes, and proteomes of 76 localized, intermediate-risk prostate cancers. We discovered that the genomic subtypes of prostate cancer converge on five proteomic subtypes, with distinct clinical trajectories. ETS fusions, the most common alteration in prostate tumors, affect different genes and pathways in the proteome and transcriptome. Globally, mRNA abundance changes explain only ∼10% of protein abundance variability. As a result, prognostic biomarkers combining genomic or epigenomic features with proteomic ones significantly outperform biomarkers comprised of a single data type.Graphical Abstract
Source: Cancer Cell - Category: Cancer & Oncology Source Type: research