Organoid Cultures Derived from Patients with Advanced Prostate Cancer

被引：1217

作者：

Gao, Dong ^{[1
]}

Vela, Ian ^{[1
,2
]}

Sboner, Andrea ^{[3
,4
,5
,10
]}

Iaquinta, Phillip J. ^{[1
]}

Karthaus, Wouter R. ^{[6
,7
]}

Gopalan, Anuradha ^{[8
]}

Dowling, Catherine ^{[1
,2
]}

Wanjala, Jackline N. ^{[1
]}

Undvall, Eva A. ^{[9
]}

Arora, Vivek K. ^{[1
,13
]}

Wongvipat, John ^{[1
]}

Kossai, Myriam ^{[5
,10
]}

Ramazanoglu, Sinan ^{[3
,5
,10
]}

Barboza, Luendreo P. ^{[1
]}

Di, Wei ^{[1
]}

Cao, Zhen ^{[1
]}

Zhang, Qi Fan ^{[1
]}

Sirota, Inna ^{[1
]}

Ran, Leili ^{[1
]}

MacDonald, Theresa Y. ^{[5
,10
]}

Beltran, Himisha ^{[4
,5
,12
]}

Mosquera, Juan-Miguel ^{[5
,10
]}

Touijer, Karim A. ^{[2
]}

Scardino, Peter T. ^{[2
]}

Laudone, Vincent P. ^{[2
]}

Curtis, Kristen R.

Rathkopf, Dana E. ^{[5
,12
,13
]}

Morris, Michael J. ^{[5
,12
,13
]}

Danila, Daniel C. ^{[5
,12
,13
]}

Slovin, Susan F. ^{[5
,12
,13
]}

Solomon, Stephen B. ^{[11
]}

Eastham, James A. ^{[2
]}

Chi, Ping ^{[1
,5
,12
,13
]}

Carver, Brett ^{[1
,2
]}

Rubin, Mark A. ^{[4
,5
,10
]}

Scher, Howard I. ^{[5
,12
,13
]}

Clevers, Hans ^{[6
,7
]}

Sawyers, Charles L. ^{[1
,14
]}

Chen, Yu ^{[1
,5
,12
,13
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10065 USA

[3] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY 10065 USA

[4] Weill Cornell Med Coll, Inst Precis Med, New York, NY 10065 USA

[5] New York Presbyterian Hosp, New York, NY 10065 USA

[6] Royal Netherlands Acad Arts & Sci, Hubrecht Inst, NL-3584 CT Utrecht, Netherlands

[7] Univ Med Ctr Utrecht, NL-3584 CT Utrecht, Netherlands

[8] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[9] Mem Sloan Kettering Canc Ctr, Lab Med, New York, NY 10065 USA

[10] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA

[11] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA

[12] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA

[13] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[14] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

CELL | 2014年 / 159卷 / 01期

基金：

美国国家卫生研究院;

关键词：

IN-VITRO EXPANSION; CELL-LINE; MOLECULAR CHARACTERIZATION; INCREASED SURVIVAL; DRUG-SENSITIVITY; CARCINOMA; IDENTIFICATION; REARRANGEMENT; CASTRATION; MODEL;

D O I：

10.1016/j.cell.2014.08.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：176 / 187

页数：12

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