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 MacDonald; Himisha 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

doi:10.1016/j.cell.2014.08.016

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

1126 Citations (Scopus)

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 language	English
Pages (from-to)	176-87
Number of pages	12
Journal	Cell
Volume	159
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2014.08.016
Publication status	Published - 25 Sept 2014

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Gao, D., Vela, I., Sboner, A., Iaquinta, P. J., Karthaus, W. R., Gopalan, A., Dowling, C., Wanjala, J. N., Undvall, E. A., Arora, V. K., Wongvipat, J., Kossai, M., Ramazanoglu, S., Barboza, L. P., Di, W., Cao, Z., Zhang, Q. F., Sirota, I., Ran, L., ... Chen, Y. (2014). Organoid cultures derived from patients with advanced prostate cancer. Cell, 159(1), 176-87. https://doi.org/10.1016/j.cell.2014.08.016

@article{8b1e18efa04146dfa31ee5e4d70ab6c3,

title = "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.",

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

year = "2014",

month = sep,

day = "25",

doi = "10.1016/j.cell.2014.08.016",

language = "English",

volume = "159",

pages = "176--87",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

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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-M, Touijer, KA, Scardino, PT, Laudone, VP, Curtis, KR, Rathkopf, DE, Morris, MJ, Danila, DC, Slovin, SF, Solomon, SB, Eastham, JA, Chi, P, Carver, B, Rubin, MA, Scher, HI, Clevers, H, Sawyers, CL & Chen, Y 2014, 'Organoid cultures derived from patients with advanced prostate cancer', Cell, vol. 159, no. 1, pp. 176-87. https://doi.org/10.1016/j.cell.2014.08.016

TY - JOUR

T1 - Organoid cultures derived from patients with advanced prostate cancer

AU - Gao, Dong

AU - Vela, Ian

AU - Sboner, Andrea

AU - Iaquinta, Phillip J

AU - Karthaus, Wouter R

AU - Gopalan, Anuradha

AU - Dowling, Catherine

AU - Wanjala, Jackline N

AU - Undvall, Eva A

AU - Arora, Vivek K

AU - Wongvipat, John

AU - Kossai, Myriam

AU - Ramazanoglu, Sinan

AU - Barboza, Luendreo P

AU - Di, Wei

AU - Cao, Zhen

AU - Zhang, Qi Fan

AU - Sirota, Inna

AU - Ran, Leili

AU - MacDonald, Theresa Y

AU - Beltran, Himisha

AU - Mosquera, Juan-Miguel

AU - Touijer, Karim A

AU - Scardino, Peter T

AU - Laudone, Vincent P

AU - Curtis, Kristen R

AU - Rathkopf, Dana E

AU - Morris, Michael J

AU - Danila, Daniel C

AU - Slovin, Susan F

AU - Solomon, Stephen B

AU - Eastham, James A

AU - Chi, Ping

AU - Carver, Brett

AU - Rubin, Mark A

AU - Scher, Howard I

AU - Clevers, Hans

AU - Sawyers, Charles L

AU - Chen, Yu

PY - 2014/9/25

Y1 - 2014/9/25

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2014.08.016

DO - 10.1016/j.cell.2014.08.016

M3 - Article

C2 - 25201530

SN - 0092-8674

VL - 159

SP - 176

EP - 187

JO - Cell

JF - Cell

IS - 1

ER -

Organoid cultures derived from patients with advanced prostate cancer

Abstract

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