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Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes

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, i...

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Autores principales: Liu, Deli, Shoag, Jonathan E., Poliak, Daniel, Goueli, Ramy S., Ravikumar, Vaishali, Redmond, David, Vosoughi, Aram, Fontugne, Jacqueline, Pan, Heng, Lee, Daniel, Thomas, Domonique, Salari, Keyan, Wang, Zongwei, Romanel, Alessandro, Te, Alexis, Lee, Richard, Chughtai, Bilal, Olumi, Aria F., Mosquera, Juan Miguel, Demichelis, Francesca, Elemento, Olivier, Rubin, Mark A., Sboner, Andrea, Barbieri, Christopher E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181734/
https://www.ncbi.nlm.nih.gov/pubmed/32332823
http://dx.doi.org/10.1038/s41467-020-15913-6
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author Liu, Deli
Shoag, Jonathan E.
Poliak, Daniel
Goueli, Ramy S.
Ravikumar, Vaishali
Redmond, David
Vosoughi, Aram
Fontugne, Jacqueline
Pan, Heng
Lee, Daniel
Thomas, Domonique
Salari, Keyan
Wang, Zongwei
Romanel, Alessandro
Te, Alexis
Lee, Richard
Chughtai, Bilal
Olumi, Aria F.
Mosquera, Juan Miguel
Demichelis, Francesca
Elemento, Olivier
Rubin, Mark A.
Sboner, Andrea
Barbieri, Christopher E.
author_facet Liu, Deli
Shoag, Jonathan E.
Poliak, Daniel
Goueli, Ramy S.
Ravikumar, Vaishali
Redmond, David
Vosoughi, Aram
Fontugne, Jacqueline
Pan, Heng
Lee, Daniel
Thomas, Domonique
Salari, Keyan
Wang, Zongwei
Romanel, Alessandro
Te, Alexis
Lee, Richard
Chughtai, Bilal
Olumi, Aria F.
Mosquera, Juan Miguel
Demichelis, Francesca
Elemento, Olivier
Rubin, Mark A.
Sboner, Andrea
Barbieri, Christopher E.
author_sort Liu, Deli
collection PubMed
description 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.
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spelling pubmed-71817342020-04-29 Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes Liu, Deli Shoag, Jonathan E. Poliak, Daniel Goueli, Ramy S. Ravikumar, Vaishali Redmond, David Vosoughi, Aram Fontugne, Jacqueline Pan, Heng Lee, Daniel Thomas, Domonique Salari, Keyan Wang, Zongwei Romanel, Alessandro Te, Alexis Lee, Richard Chughtai, Bilal Olumi, Aria F. Mosquera, Juan Miguel Demichelis, Francesca Elemento, Olivier Rubin, Mark A. Sboner, Andrea Barbieri, Christopher E. Nat Commun Article 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. Nature Publishing Group UK 2020-04-24 /pmc/articles/PMC7181734/ /pubmed/32332823 http://dx.doi.org/10.1038/s41467-020-15913-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Deli
Shoag, Jonathan E.
Poliak, Daniel
Goueli, Ramy S.
Ravikumar, Vaishali
Redmond, David
Vosoughi, Aram
Fontugne, Jacqueline
Pan, Heng
Lee, Daniel
Thomas, Domonique
Salari, Keyan
Wang, Zongwei
Romanel, Alessandro
Te, Alexis
Lee, Richard
Chughtai, Bilal
Olumi, Aria F.
Mosquera, Juan Miguel
Demichelis, Francesca
Elemento, Olivier
Rubin, Mark A.
Sboner, Andrea
Barbieri, Christopher E.
Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes
title Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes
title_full Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes
title_fullStr Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes
title_full_unstemmed Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes
title_short Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes
title_sort integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181734/
https://www.ncbi.nlm.nih.gov/pubmed/32332823
http://dx.doi.org/10.1038/s41467-020-15913-6
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