MSKCC Prostate Cancer Integrative Genomic Profiling

Overview

Integrative genomic profiling of 218 prostate cancers (181 primary tumors and 37 metastases) plus 12 cell lines/xenografts from Memorial Sloan Kettering Cancer Center. The dataset is publicly available on cBioPortal as prad_mskcc (GEO accession GSE21032). All samples had at least 70% tumor content; median follow-up approximately 5 years. The study combined DNA copy number, mRNA/miRNA expression, and targeted exon resequencing to characterize the genomic landscape of prostate cancer.

Composition

  • Cancer type: PRAD
  • 218 prostate tumors: 181 primary + 37 metastases; 12 cell lines/xenografts
  • Platforms: Agilent 244K aCGH, Affymetrix Human Exon 1.0 ST (mRNA), Agilent miRNA V2
  • Targeted resequencing: Sanger exon resequencing of 138 genes in 80 tumors; iPLEX Sequenom for 22 oncogene hotspots in 156 tumors
  • Key clinical fields: Gleason score, pathological stage, biochemical recurrence, castration-resistance status

Assays / panels (linked)

Papers using this cohort

  • PMID:20579941 — Taylor et al. 2010, integrative genomic profiling paper defining the cohort

Notable findings derived from this cohort

  • NCOA2 amplification at 8q13.3 in ~11% of tumors (24.3% of metastases); overexpression correlated with enhanced AR transcriptional output (p < 0.0001) PMID:20579941
  • TMPRSS2-ERG fusion present in 52% of tumors; associated with a novel prostate-specific 3p14 deletion implicating FOXP1, RYBP, and SHQ1 as cooperative tumor suppressors PMID:20579941
  • PI3K pathway altered in 42% of primary tumors and 100% of metastases; AR pathway altered in 56% of primaries and 100% of metastases PMID:20579941
  • Unsupervised CNA-based hierarchical clustering identified 6 prognostic subgroups independent of Gleason score PMID:20579941
  • Low somatic mutation rate (~0.31 mutations/Mb); TP53 and PTEN primarily lost through copy-number deletion rather than point mutation PMID:20579941
  • Used as a validation cohort for somatic copy-number alteration and mutation profiling in metastatic castration-resistant prostate cancer PMID:25024180
  • Referenced as a comparison cohort (218 cases, Taylor 2010) in the MSK-IMPACT prospective prostate cancer profiling study for contextualizing DDR gene alteration frequencies PMID:28825054.
  • Used (Taylor 2010 / GSE21034, n=140) in a fixed-effects BCR meta-analysis across CPGEA / MSKCC / TCGA / DKFZ yielding HR=2.49 (1.85–3.35, P=1.81e-9) for the NOL10 cell-cycle signature; also used for NOL10–EMT/AR signature correlation (n=150) PMID:28927585.

Sources

  • PMID:20579941 — Taylor et al., “Integrative genomic profiling of human prostate cancer,” Cancer Cell 2010
  • GEO: GSE21032
  • cBioPortal: https://www.cbioportal.org/study/summary?id=prad_mskcc

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