MSKCC Prostate Cancer Organoids (Gao/Chen 2014)

Overview

Seven patient-derived 3D organoid lines (MSK-PCa1–7) established from metastatic biopsies (n=6) and one circulating-tumor-cell sample from men with advanced prostate cancer (PRAD) at Memorial Sloan Kettering Cancer Center (IRB 90-040/06-107; Dec 2012–Nov 2013). The lines were profiled by whole-exome sequencing, RNA-seq, and 1M array-CGH. Establishment efficiency was ~15–20% from metastatic biopsies.

Composition

  • 7 organoid lines from advanced PRAD; 6 from metastatic biopsies (bone, lymph node, soft tissue, pleural effusion), 1 from CTCs.
  • Source biopsy pool: 32 metastasis samples (18 bone, 9 lymph node, 2 liver, 1 brain, 1 bladder, 1 pleural effusion) and 17 blood draws.
  • Assays: whole-exome-seq (Agilent SureSelectXT2, ~142× mean), rna-seq, array-cgh-agilent-1m.
  • Reference genome: hg19.

Assays / panels (linked)

Papers using this cohort

Notable findings derived from this cohort

  • 6/7 organoid lines carry focal homozygous deletion of PTEN; TP53 is mutated with complete loss of function in 4/7 lines; CHD1 is homozygously deleted in 3/7 lines (MSK-PCa2, PCa4, PCa7) PMID:25201530.
  • MSK-PCa7 carries the first in vitro model of a SPOP F133L substrate-recognition-domain hotspot mutation; MSK-PCa1 and MSK-PCa3 carry TMPRSS2-ERG interstitial deletion PMID:25201530.
  • AR-amplified MSK-PCa2 was sensitive to enzalutamide (IC50 ~50 nM) and to everolimus; combined enzalutamide + everolimus significantly enhanced xenograft response over enzalutamide alone PMID:25201530.

Sources

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