MSKCC Prostate Cancer CNA Burden Cohort (2014)

Overview

Contemporary cohort of 104 radical prostatectomy cases with matched normals, profiled at Memorial Sloan Kettering Cancer Center by high-resolution array comparative genomic hybridization (Agilent 1M-feature array-CGH). Assembled by Hieronymus et al. (2014) to validate CNA burden as a prognostic biomarker for biochemical recurrence (BCR) in primary prostate cancer, complementing the earlier 168-case prad_mskcc cohort (Taylor et al. 2010). Raw data deposited at GEO (GSE54691) and the MSKCC Prostate Cancer Genomics Data Portal.

Composition

  • Cancer type: primary prostate adenocarcinoma (PRAD)
  • 104 prostatectomy cases + matched germline normals; snap-frozen samples with >70% tumor content
  • Median follow-up 6 years; BCR events n=24 (53 per 1,000 person-years); metastatic events n=3
  • Key clinical variables: pretreatment PSA, biopsy and pathology Gleason score, postoperative Stephenson 5-year nomogram

Assays / panels (linked)

  • array-cgh-agilent-1m: Agilent 1M-feature array-CGH on snap-frozen tissue with Promega pooled-reference DNA; aligned to hg19
  • Feasibility sub-study: 4 FFPE needle biopsies profiled by agilent-244k and low-pass whole-genome-seq (1–3× via Illumina HiSeq 2000, 100 bp paired-end, BWA alignment, hg19)

Papers using this cohort

  • PMID:25024180 — Hieronymus et al. 2014, “Copy number alteration burden predicts prostate cancer relapse”

Notable findings derived from this cohort

  • CNA burden (fraction of autosomal genome with copy-number change) is associated with BCR: HR 1.05 per 1% CNA (95% CI 1.01–1.09, P=0.008); stratified at the 5.41% threshold, HR for BCR is 3.85 (P=0.001) PMID:25024180
  • CNA burden remains prognostic for BCR after adjustment for pretreatment PSA, biopsy Gleason score, pathology Gleason score, and the postoperative Stephenson 5-year nomogram (HR 1.05, P=0.011) PMID:25024180
  • In the Gleason 7 intermediate-risk subgroup, CNA burden ranges 0.003–50%; univariate HR for BCR is 1.06 (P=0.017), persisting after PSA and Stephenson adjustment PMID:25024180
  • Low-pass WGS (1–3×) of FFPE needle biopsies yielded CNA profiles concordant with high-resolution array-CGH, including focal 3p13 deletions and arm-level gains/losses PMID:25024180

Sources

  • GEO: GSE54691
  • cBioPortal studyId: prad_mskcc_2014

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