title: Organoid cultures derived from patients with advanced prostate cancer.
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.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Ian
authors.initials: I
authors.lastname: Vela
authors.affiliation: 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.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sboner
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Iaquinta
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
authors.forename: Wouter R
authors.initials: WR
authors.lastname: Karthaus
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Gopalan
authors.affiliation: 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.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dowling
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Jackline N
authors.initials: JN
authors.lastname: Wanjala
authors.affiliation: Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Eva A
authors.initials: EA
authors.lastname: Undvall
authors.affiliation: 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.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Arora
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: John
authors.initials: J
authors.lastname: Wongvipat
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Kossai
authors.affiliation: 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.
authors.forename: Sinan
authors.initials: S
authors.lastname: Ramazanoglu
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Luendreo P
authors.initials: LP
authors.lastname: Barboza
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Di
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Qi Fan
authors.initials: QF
authors.lastname: Zhang
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Inna
authors.initials: I
authors.lastname: Sirota
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Leili
authors.initials: L
authors.lastname: Ran
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Theresa Y
authors.initials: TY
authors.lastname: MacDonald
authors.affiliation: 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.
authors.forename: Himisha
authors.initials: H
authors.lastname: Beltran
authors.affiliation: 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.
authors.forename: Juan-Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.affiliation: Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Karim A
authors.initials: KA
authors.lastname: Touijer
authors.affiliation: Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.affiliation: Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Laudone
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Curtis
authors.affiliation: 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.
authors.forename: Dana E
authors.initials: DE
authors.lastname: Rathkopf
authors.affiliation: 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.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.affiliation: 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.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Danila
authors.affiliation: 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.
authors.forename: Susan F
authors.initials: SF
authors.lastname: Slovin
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Solomon
authors.affiliation: Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Eastham
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Chi
authors.affiliation: 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.
authors.forename: Brett
authors.initials: B
authors.lastname: Carver
authors.affiliation: 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.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.affiliation: 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.
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.affiliation: Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, 3584 CT, Utrecht, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: 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.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
authors.affiliation: 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.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D046508:Culture Techniques; D064593:Heterografts; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology; D009940:Organoids / Q000473:pathology; D010600:Pharmacology / Q000379:methods; D011471:Prostatic Neoplasms / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins