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 Demichelis, Olivier Elemento, Mark A. Rubin, Andrea Sboner () and Christopher E. Barbieri ()
Additional contact information
Deli Liu: Weill Cornell Medicine
Jonathan E. Shoag: Weill Cornell Medicine
Daniel Poliak: Weill Cornell Medicine
Ramy S. Goueli: Weill Cornell Medicine
Vaishali Ravikumar: Weill Cornell Medicine
David Redmond: Weill Cornell Medicine
Aram Vosoughi: Weill Cornell Medical College
Jacqueline Fontugne: Englander Institute for Precision Medicine of Weill Cornell Medicine and NewYork-Presbyterian Hospital
Heng Pan: Englander Institute for Precision Medicine of Weill Cornell Medicine and NewYork-Presbyterian Hospital
Daniel Lee: Weill Cornell Medicine
Domonique Thomas: Weill Cornell Medicine
Keyan Salari: Harvard Medical School
Zongwei Wang: Harvard Medical School
Alessandro Romanel: Computational and Integrative Biology (CIBIO)
Alexis Te: Weill Cornell Medicine
Richard Lee: Weill Cornell Medicine
Bilal Chughtai: Weill Cornell Medicine
Aria F. Olumi: Harvard Medical School
Juan Miguel Mosquera: Weill Cornell Medical College
Francesca Demichelis: Computational and Integrative Biology (CIBIO)
Olivier Elemento: Weill Cornell Medical College
Mark A. Rubin: Englander Institute for Precision Medicine of Weill Cornell Medicine and NewYork-Presbyterian Hospital
Andrea Sboner: Weill Cornell Medicine
Christopher E. Barbieri: Weill Cornell Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15913-6

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