Cell
Volume 159, Issue 1, 25 September 2014, Pages 176-187
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Organoid Cultures Derived from Patients with Advanced Prostate Cancer

https://doi.org/10.1016/j.cell.2014.08.016Get rights and content
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Highlights

  • Generation of prostate cancer organoids from metastasis and circulating tumor cells

  • Organoids retain the histological and molecular features of the patient specimen

  • Organoids recapitulate the diversity of castration-resistant prostate cancer

  • Organoid lines can be used for drug studies in vitro and as xenografts in vivo

Summary

The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.

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