title: Genomic Copy Number Variations in the Genomes of Leukocytes Predict Prostate Cancer Clinical Outcomes.
abstract: Accurate prediction of prostate cancer clinical courses remains elusive. In this study, we performed whole genome copy number analysis on leukocytes of 273 prostate cancer patients using Affymetrix SNP6.0 chip. Copy number variations (CNV) were found across all chromosomes of the human genome. An average of 152 CNV fragments per genome was identified in the leukocytes from prostate cancer patients. The size distributions of CNV in the genome of leukocytes were highly correlative with prostate cancer aggressiveness. A prostate cancer outcome prediction model was developed based on large size ratio of CNV from the leukocyte genomes. This prediction model generated an average prediction rate of 75.2%, with sensitivity of 77.3% and specificity of 69.0% for prostate cancer recurrence. When combined with Nomogram and the status of fusion transcripts, the average prediction rate was improved to 82.5% with sensitivity of 84.8% and specificity of 78.2%. In addition, the leukocyte prediction model was 62.6% accurate in predicting short prostate specific antigen doubling time. When combined with Gleason's grade, Nomogram and the status of fusion transcripts, the prediction model generated a correct prediction rate of 77.5% with 73.7% sensitivity and 80.1% specificity. To our knowledge, this is the first study showing that CNVs in leukocyte genomes are predictive of clinical outcomes of a human malignancy.
authors: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Yan P
authors: YP
authors: Yu
authors: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Silvia
authors: S
authors: Liu
authors: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Zhiguang
authors: Z
authors: Huo
authors: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Amantha
authors: A
authors: Martin
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Joel B
authors: JB
authors: Nelson
authors: Department of Biostatistics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: George C
authors: GC
authors: Tseng
authors: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors: Jian-Hua
authors: JH
authors: Luo
mesh_terms: D056915:DNA Copy Number Variations; D015870:Gene Expression; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D049451:Nomograms; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000235:genetics* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen