title: Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location.
abstract: Prostate cancer (PCa) subtypes based on ETS gene expression have been described. Recent studies suggest there are racial differences in tumor location, with PCa located anteriorly more often among African-American (AA) compared to Caucasian-American (CA) men. In this retrospective analysis of a multi-institutional cohort treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations among molecular subtype, race, anatomic tumor location, and androgen receptor (AR) signaling. Subtype (m-ERG(+), m-ETS(+), m-SPINK1(+), or triple-negative) was determined using distribution-based outlier analysis. AR signaling was investigated using gene expression profiling of canonical AR targets. m-ERG(+) was more common in CA than AA men (47% vs 22%, p<0.001). AA men were more likely to be m-SPINK1(+) (13% vs 7%; p=0.069) and triple-negative (50% vs 37%; p=0.043). Racial differences in molecular subtypes did not persist when tumors were analyzed by location, suggesting a biologically important relationship between tumor location and subtype. Accordingly, anterior tumor location was associated with higher Decipher scores and lower global AR signaling.
  
  
  
  This study demonstrates associations among patient race, prostate cancer molecular subtypes, and tumor location. Location-specific differences in androgen regulation may further underlie these relationships.
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: ffaisal1@jhmi.edu.
authors.forename: Farzana A
authors.initials: FA
authors.lastname: Faisal
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Debasish
authors.initials: D
authors.lastname: Sundi
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Tosoian
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Voleak
authors.initials: V
authors.lastname: Choeurng
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alshalalfa
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Ross
authors.affiliation: Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Klein
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Den
authors.affiliation: Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Dicker
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Erho
authors.affiliation: GenomeDx Biosciences, Vancouver, BC, Canada.
authors.forename: Elai
authors.initials: E
authors.lastname: Davicioni
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Lotan
authors.affiliation: Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schaeffer
mesh_terms: D001741:Black or African American / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D008297:Male; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D011944:Receptors, Androgen / Q000378:metabolism*; D012189:Retrospective Studies; D015398:Signal Transduction; D000071230:Transcriptional Regulator ERG / Q000235:genetics; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: C072312:ERG protein, human; D050783:Proto-Oncogene Proteins c-ets; D011944:Receptors, Androgen; C486642:SPINK1 protein, human; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic; D017430:Prostate-Specific Antigen
keywords: African-American; ETS gene fusion; Molecular subtype; Prostatic neoplasm; Race; SPINK1; TMPRSS2-ERG fusion