Early Detection Research Network

The Proteogenomic Landscape of Curable Prostate Cancer.

DNA 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.

Alfaro JA, Berman DM, Boutros PC, Bristow RG, Collins CC, Donmez N, Fox NS, Fraser M, Fritsch K, Heisler LE, Huang V, Ignatchenko V, Kislinger T, Kron K, Kurganovs N, Lapuk A, Livingstone J, Lupien M, Masoomian M, Murison A, Sahinalp C, Shiah YJ, Sinha A, Tetu B, Volik S, Wang J, Yao CQ, van der Kwast T

30889379

Cancer Cell, 2019, 35 (3)