Journal Article

Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes

Thomas, Domonique, Poliak, Daniel, Mosquera, Juan Miguel, Demichelis, Francesca, Rubin, Mark A., Goueli, Ramy S., Fontugne, Jacqueline, Te, Alexis, Chughtai, Bilal, Ravikumar, Vaishali, Lee, Daniel, Salari, Keyan, Liu, Deli, Shoag, Jonathan E., Elemento, Olivier, Sboner, Andrea, Olumi, Aria F., Redmond, David, Vosoughi, Aram, Romanel, Alessandro, Barbieri, Christopher E., Pan, Heng, Wang, Zongwei, Lee, Richard

2020

Overview

Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements. At the epigenetic level, global hypermethylation is the dominant process. Integrating transcriptional and methylation signatures identifies two BPH subgroups with distinct clinical features and signaling pathways, validated in two independent cohorts. Finally, mTOR inhibitors emerge as a potential subtype-specific therapeutic option, and men exposed to mTOR inhibitors show a significant decrease in prostate size. We conclude that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy. Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting aging men with limited therapeutic options. In this study, the authors describe the molecular characterization of BPH performing genomic, transcriptomic and epigenetic analysis of 18 BPH cases.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/23 / 45/61 / 45/91 / 631/114 / 631/154/555 / 631/67 / Adult / Aged / Aged, 80 and over / Aging / Benign / Biomarkers - analysis / Copy number / DNA Methylation / Enlargement / Epigenesis, Genetic / Epigenetics / Epigenomics / Genital diseases / Genomics / Humanities and Social Sciences / Humans / Hyperplasia / Inhibitors / Male / Middle Aged / multidisciplinary / Mutation / Mutation Rate / Mutation rates / Organ Size - drug effects / Organ Size - genetics / Precision Medicine - methods / Prospective Studies / Prostate / Prostate - diagnostic imaging / Prostate - drug effects / Prostate - pathology / Prostatic Hyperplasia - diagnostic imaging / Prostatic Hyperplasia - drug therapy / Prostatic Hyperplasia - genetics / Prostatic Hyperplasia - pathology / RNA-Seq / Science / Science (multidisciplinary) / Signal Transduction - drug effects / Signal Transduction - genetics / Signatures / Sirolimus - analogs & derivatives / Subgroups / Tomography, X-Ray Computed / TOR protein / TOR Serine-Threonine Kinases - antagonists & inhibitors / TOR Serine-Threonine Kinases - genetics / TOR Serine-Threonine Kinases - metabolism / Treatment Outcome / Urological Agents - pharmacology / Urological Agents - therapeutic use / Whole Genome Sequencing