Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • April 24, 2020

Research

keywords

  • Prostate
  • Prostatic Hyperplasia
  • TOR Serine-Threonine Kinases
  • Urological Agents

Identity

PubMed Central ID

  • PMC7181734

Scopus Document Identifier

  • 85083830012

Digital Object Identifier (DOI)

  • 10.1056/NEJM199210223271701

PubMed ID

  • 32332823

Additional Document Info

volume

  • 11

issue

  • 1