Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes.

TitleIntegrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes.
Publication TypeJournal Article
Year of Publication2020
AuthorsLiu D, Shoag JE, Poliak D, Goueli RS, Ravikumar V, Redmond D, Vosoughi A, Fontugne J, Pan H, Lee D, Thomas D, Salari K, Wang Z, Romanel A, Te A, Lee R, Chughtai B, Olumi AF, Mosquera JMiguel, Demichelis F, Elemento O, Rubin MA, Sboner A, Barbieri CE
JournalNat Commun
Date Published2020 04 24
KeywordsAdult, Aged, Aged, 80 and over, Aging, Biomarkers, DNA Methylation, Epigenesis, Genetic, Epigenomics, Genomics, Humans, Male, Middle Aged, Mutation Rate, Organ Size, Precision Medicine, Prospective Studies, Prostate, Prostatic Hyperplasia, RNA-Seq, Signal Transduction, Sirolimus, Tomography, X-Ray Computed, TOR Serine-Threonine Kinases, Treatment Outcome, Urological Agents, Whole Genome Sequencing

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.

Alternate JournalNat Commun
PubMed ID32332823
PubMed Central IDPMC7181734
Grant ListUL1 RR024996 / RR / NCRR NIH HHS / United States
P50 CA211024 / CA / NCI NIH HHS / United States