@article{5f6ba1a4d887425582634b9afa1d5652,
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.",
author = "Dong Gao and Ian Vela and Andrea Sboner and Iaquinta, {Phillip J.} and Karthaus, {Wouter R.} and Anuradha Gopalan and Catherine Dowling and Wanjala, {Jackline N.} and Undvall, {Eva A.} and Arora, {Vivek K.} and John Wongvipat and Myriam Kossai and Sinan Ramazanoglu and Barboza, {Luendreo P.} and Wei Di and Zhen Cao and Zhang, {Qi Fan} and Inna Sirota and Leili Ran and Macdonald, {Theresa Y.} and Himisha Beltran and Mosquera, {Juan Miguel} and Touijer, {Karim A.} and Scardino, {Peter T.} and Laudone, {Vincent P.} and Curtis, {Kristen R.} and Rathkopf, {Dana E.} and Morris, {Michael J.} and Danila, {Daniel C.} and Slovin, {Susan F.} and Solomon, {Stephen B.} and Eastham, {James A.} and Ping Chi and Brett Carver and Rubin, {Mark A.} and Scher, {Howard I.} and Hans Clevers and Sawyers, {Charles L.} and Yu Chen",
note = "Funding Information: We would like to thank the Prostate Cancer Foundation (PCF) for generous financial support as well as Drs. Howard Soule and Jonathon Simons for stimulating discussions. We thank the follow MSKCC core facilities: Genomics Core Laboratory (Daoqi You, Agnes Viales), and Molecular Cytology (Ning Fan and Mesruh Turkekul). We thank the National Institutes of Health (5K08CA140946, Y.C.; P50CA092629 Y.C., H.I.S., B.C., C.L.S.; CA155169-01A1, C.L.S.; 5R01CA116337, H.B. and M.A.R.), US Department of Defense (W81XWH-10-1-0197, Y.C.; W81XWH-09-1-0147, H.I.S.), Movember Foundation (Y.C., D.C.D., B.C., S.B.S., C.L.S.), the Geoffrey Beene Cancer Center (Y.C., B.C.) the STARR Cancer Consortium for funding (I8-A722, Y.C., H.B., M.A.R.). Research supported by a Stand Up To Cancer – Prostate Cancer Foundation Prostate Dream Team Translational Research Grant (SU2C-AACR-DT0712). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. H.C. is an inventor on several parents related to this work. Publisher Copyright: {\textcopyright} 2014 Elsevier Inc.",
year = "2014",
month = sep,
day = "25",
doi = "10.1016/j.cell.2014.08.016",
language = "English",
volume = "159",
pages = "176--187",
journal = "Cell",
issn = "0092-8674",
number = "1",
}