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.

journal_name

Cell

journal_title

Cell

authors

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 J

doi

10.1016/j.cell.2014.08.016

subject

Has Abstract

pub_date

2014-09-25 00:00:00

pages

176-187

issue

1

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(14)01047-2

journal_volume

159

pub_type

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