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| Status |
Public on Jun 30, 2014 |
| Title |
Copy number alteration burden predicts prostate cancer relapse: Agilent 1M aCGH data for human primary prostate cancer samples |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by genome tiling array
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| Summary |
Prostate cancer is the most common malignancy in men. Yet, the modest benefit of treatment highlights the unmet need for prognostic biomarkers in prostate cancer (1). Few large prostate oncogenome resources currently exist that combine the molecular and clinical outcome data necessary for prognostic discovery. To determine the extent to which genomic aberrations reflect the risk of prostate cancer-specific outcomes, we profiled more than 100 primary prostate cancers with long-term follow-up for genome-wide copy number alterations (CNA). We also updated the long-term clinical outcome (median 8 years) of an additional independent cohort of 181 primary prostate cancers that we previously profiled for CNA and expression changes (2). Together, we found that CNA burden across the genome, defined as the percent of the tumor genome affected by CNA, is prognostic for recurrence and metastasis in these two cohorts. This prognostic significance of CNA is independent of Gleason grade, a major existing histopathological prognostic variable in prostate cancer. Moreover, in intermediate-risk Gleason 7 prostate cancers that show a wide range of outcomes, CNA burden is also prognostic for biochemical recurrence, independent of prostate-specific antigen or nomogram score. CNA burden therefore has the potential to stratify patients by their risk of recurrence in an otherwise intermediate risk subpopulation. We further demonstrate that CNA burden can be established in diagnostic FFPE needle biopsies using low-input whole genome sequencing. Together, this work highlights the potential of oncogenomics to identify useful and clinically amenable prognostic factors that may inform prostate cancer outcome and treatment.
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| Overall design |
Human prostate samples were profiled on Agilent 1M aCGH arrays per manufacturer's instructions. A pooled reference normal DNA was used as the reference.
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| Contributor(s) |
Hieronymus H, Schultz N, Taylor BS, Sawyers CL |
| Citation(s) |
25024180 |
| Submission date |
Feb 05, 2014 |
| Last update date |
Aug 01, 2014 |
| Contact name |
Nikolaus Schultz |
| E-mail(s) |
schultz@cbio.mskcc.org
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| Phone |
646-888-2604
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| Organization name |
Memorial Sloan-Kettering Cancer Center
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| Department |
Computational Biology Center
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| Street address |
1275 York Ave, Box 460
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL8737 |
Agilent-021529 Human CGH Whole Genome Microarray 1x1M (G4447A) (Probe Name version) |
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| Samples (104)
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| Relations |
| BioProject |
PRJNA237482 |
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