TY - JOUR
T1 - Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes
AU - Liu, Deli
AU - Shoag, Jonathan E.
AU - Poliak, Daniel
AU - Goueli, Ramy S.
AU - Ravikumar, Vaishali
AU - Redmond, David
AU - Vosoughi, Aram
AU - Fontugne, Jacqueline
AU - Pan, Heng
AU - Lee, Daniel
AU - Thomas, Domonique
AU - Salari, Keyan
AU - Wang, Zongwei
AU - Romanel, Alessandro
AU - Te, Alexis
AU - Lee, Richard
AU - Chughtai, Bilal
AU - Olumi, Aria F.
AU - Mosquera, Juan Miguel
AU - Demichelis, Francesca
AU - Elemento, Olivier
AU - Rubin, Mark A.
AU - Sboner, Andrea
AU - Barbieri, Christopher E.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85083830012&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083830012&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-15913-6
DO - 10.1038/s41467-020-15913-6
M3 - Article
C2 - 32332823
AN - SCOPUS:85083830012
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1987
ER -