Prostate Adenocarcinoma — TCGA 2015

Overview

Integrated multi-platform molecular characterization of 333 primary prostate adenocarcinomas (PRAD) from radical prostatectomy specimens, assembled by The Cancer Genome Atlas (TCGA) Research Network. The cohort (originally 425 cases, reduced to 333 after pathology and quality-control review) was profiled by whole-exome and whole-genome sequencing, SNP arrays, DNA methylation arrays, mRNA and miRNA sequencing, and reverse-phase protein arrays (RPPA). Reference genome hg19.

Composition

  • 333 primary prostate adenocarcinomas (radical prostatectomy; final cohort after QC review from 425 initial cases).
  • 19 matched non-malignant adjacent prostate samples profiled for methylation and RNA/miRNA expression.
  • Cancer type: PRAD (prostate adenocarcinoma).
  • Average follow-up under two years; outcomes analysis was not performed.

Assays / panels (linked)

Papers using this cohort

  • PMID:26544944 — The Cancer Genome Atlas Research Network 2015, “The Molecular Taxonomy of Primary Prostate Cancer,” Cell.

Notable findings derived from this cohort

  • Seven mutually exclusive molecular subtypes capture 74% of primary prostate cancers: ETS-family fusions — ERG 46%, ETV1 8%, ETV4 4%, FLI1 1% — and hotspot mutations in SPOP 11%, FOXA1 3%, IDH1 1% PMID:26544944.
  • Median mutational burden 0.94 mutations/Mb (~19 non-synonymous mutations/tumor); 13 significantly mutated genes at q < 0.1, including SPOP, TP53, FOXA1, PTEN, MED12, CDKN1B, ATM PMID:26544944.
  • Homozygous PTEN deletion in 15% — one of the highest rates across TCGA tumor types; BRCA2 loss almost always co-occurred with RB1 loss at 13q PMID:26544944.
  • DNA repair gene inactivation in 19% of tumors (BRCA2, BRCA1, CDK12, ATM, FANCD2, RAD51C), with therapeutic relevance for PARP inhibitors such as olaparib PMID:26544944.
  • IDH1 R132 mutations define a CIMP-like epigenetic subgroup with greater genome-wide hypermethylation than IDH1-mutant GBM or AML, associated with younger age and ETS/SPOP-wild-type status PMID:26544944.
  • PI3K/MAPK pathway lesions in ~25% of tumors; AR splice variants including AR-V7 detectable at low levels in hormone-naive primary tumors PMID:26544944.
  • SPOP and FOXA1 mutations confer highest AR transcriptional activity; SPOP-mutant tumors showed distinct co-mutation landscape (HEXA silencing, no ETS fusions) PMID:26544944.
  • Served as a comparison primary-prostate-cancer cohort (333 cases) in the MSK-IMPACT prospective profiling study; locoregional MSK-IMPACT tumors showed higher TP53 and FOXA1 frequencies than TCGA primaries, reflecting selection bias toward cases that subsequently recurred or metastasized PMID:28825054.

Sources

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