| Literature DB >> 25201530 |
Dong Gao1, Ian Vela2, Andrea Sboner3, Phillip J Iaquinta1, Wouter R Karthaus4, Anuradha Gopalan5, Catherine Dowling2, Jackline N Wanjala1, Eva A Undvall6, Vivek K Arora7, John Wongvipat1, Myriam Kossai8, Sinan Ramazanoglu9, Luendreo P Barboza1, Wei Di1, Zhen Cao1, Qi Fan Zhang1, Inna Sirota1, Leili Ran1, Theresa Y MacDonald8, Himisha Beltran10, Juan-Miguel Mosquera11, Karim A Touijer12, Peter T Scardino12, Vincent P Laudone12, Kristen R Curtis13, Dana E Rathkopf14, Michael J Morris14, Daniel C Danila14, Susan F Slovin14, Stephen B Solomon15, James A Eastham12, Ping Chi16, Brett Carver2, Mark A Rubin11, Howard I Scher14, Hans Clevers4, Charles L Sawyers17, Yu Chen18.
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.Entities:
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Year: 2014 PMID： 25201530 PMCID： PMC4237931 DOI： 10.1016/j.cell.2014.08.016
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582