Organoid cultures derived from patients with advanced prostate cancer

Dong Gao, Ian Vela, Andrea Sboner, Phillip J Iaquinta, Wouter R Karthaus, Anuradha Gopalan, Catherine Dowling, Jackline N Wanjala, Eva A Undvall, Vivek K Arora, John Wongvipat, Myriam Kossai, Sinan Ramazanoglu, Luendreo P Barboza, Wei Di, Zhen Cao, Qi Fan Zhang, Inna Sirota, Leili Ran, Theresa Y MacDonaldHimisha Beltran, Juan-Miguel Mosquera, Karim A Touijer, Peter T Scardino, Vincent P Laudone, Kristen R Curtis, Dana E Rathkopf, Michael J Morris, Daniel C Danila, Susan F Slovin, Stephen B Solomon, James A Eastham, Ping Chi, Brett Carver, Mark A Rubin, Howard I Scher, Hans Clevers, Charles L Sawyers, Yu Chen

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)176-87
Number of pages12
JournalCell
Volume159
Issue number1
DOIs
Publication statusPublished - 25 Sep 2014

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