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.
journal_name
Celljournal_title
Cellauthors
Gao D,Vela I,Sboner A,Iaquinta PJ,Karthaus WR,Gopalan A,Dowling C,Wanjala JN,Undvall EA,Arora VK,Wongvipat J,Kossai M,Ramazanoglu S,Barboza LP,Di W,Cao Z,Zhang QF,Sirota I,Ran L,MacDonald TY,Beltran H,Mosquera Jdoi
10.1016/j.cell.2014.08.016subject
Has Abstractpub_date
2014-09-25 00:00:00pages
176-187issue
1eissn
0092-8674issn
1097-4172pii
S0092-8674(14)01047-2journal_volume
159pub_type
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