Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes

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

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Article number1987
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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