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Cell. 2014 Sep 25;159(1):176-187. doi: 10.1016/j.cell.2014.08.016. Epub 2014 Sep 4.

Organoid cultures derived from patients with advanced prostate cancer.

Author information

1
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
2
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
3
Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA; Institute for Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
4
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
5
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
6
Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
7
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
8
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
9
Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
10
Institute for Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
11
Institute for Precision Medicine of Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
12
Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
13
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
14
Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
15
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
16
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
17
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: sawyersc@mskcc.org.
18
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: cheny1@mskcc.org.

Abstract

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.

PMID:
25201530
PMCID:
PMC4237931
DOI:
10.1016/j.cell.2014.08.016
[Indexed for MEDLINE]
Free PMC Article
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