title: Chromosome 8 markers of metastatic prostate cancer in African American men: gain of the MIR151 gene and loss of the NKX3-1 gene.
abstract: BACKGROUND
  Radical prostatectomy (RP) is not curative if patients have undetected metastatic prostate cancer. Markers that indicate the presence of metastatic disease would identify men who may benefit from systemic adjuvant therapy. Our approach was to analyze the primary tumors of men with metastatic disease versus organ-confined disease to identify molecular changes that distinguish between these groups.
  
  
  METHODS
  Patients were identified based on long-term follow-up of serum prostate specific antigen (PSA) levels following RP. We compared the tumors of African American (AA) men with undetectable serum PSA for >9 year after RP (good outcome) versus those of AA men with a rising PSA and recurrence after radiation or androgen ablation or both (poor outcome). We used real-time quantitative PCR to assay gene copy number alterations in tumor DNA relative to patient-matched non-tumor DNA isolated from paraffin-embedded tissue. We assayed several genes located in the specific regions of chromosome 8p and 8q that frequently undergo loss and/or gain, respectively, in prostate cancer, and the androgen receptor gene at Xq12.
  
  
  RESULTS
  Gain of the MIR151 gene at 8q24.3 (in 33% of poor outcome vs. 6% of good outcome tumors) and/or loss of the NKX3-1 gene at 8p21.2 (in 39% of poor outcome vs. 11% of good outcome tumors) affected 67% of poor outcome tumors, compared to only 17% of good outcome tumors.
  
  
  CONCLUSIONS
  Copy number gain of the MIR151 gene and/or loss of the NKX3-1 gene in the primary tumor may indicate the presence of metastatic disease.
authors: Vattikuti Urology Institute, Henry Ford Hospital, Detroit, Michigan 48202-3450, USA.
authors: Nandita
authors: N
authors: Barnabas
authors: Lihua
authors: L
authors: Xu
authors: Adnan
authors: A
authors: Savera
authors: Zizheng
authors: Z
authors: Hou
authors: Evelyn R
authors: ER
authors: Barrack
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005500:Follow-Up Studies; D017353:Gene Deletion; D018628:Gene Dosage; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000532:radiotherapy; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C548886:MIRN151a microRNA, human; D035683:MicroRNAs; C491178:NKX3-1 protein, human; D014157:Transcription Factors; D017430:Prostate-Specific Antigen