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Organoid cultures derived from patients with advanced prostate cancer

Gao, Dong; Vela, Ian; Sboner, Andrea; Iaquinta, Phillip J; Karthaus, Wouter R; Gopalan, Anuradha; Dowling, Catherine; Wanjala, Jackline N; Undvall, Eva A LU and Arora, Vivek K, et al. (2014) In Cell 159(1). p.176-187
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... (More)

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.

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Culture Techniques, Heterografts, Humans, Male, Neoplasm Metastasis, Organoids, Pharmacology, Prostatic Neoplasms, Tumor Suppressor Proteins, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
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Cell
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159
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1
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12 pages
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Cell Press
external identifiers
  • scopus:84907554319
ISSN
1097-4172
DOI
10.1016/j.cell.2014.08.016
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English
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0170e4c5-f989-44a0-bc6f-9bb05919f3dd
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2017-12-08 10:40:02
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@article{0170e4c5-f989-44a0-bc6f-9bb05919f3dd,
  abstract     = {<p>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.</p>},
  author       = {Gao, Dong and Vela, Ian and Sboner, Andrea and Iaquinta, Phillip J and Karthaus, Wouter R and Gopalan, Anuradha and Dowling, Catherine and Wanjala, Jackline N and Undvall, Eva A and Arora, Vivek K and Wongvipat, John and Kossai, Myriam and Ramazanoglu, Sinan and Barboza, Luendreo P and Di, Wei and Zhang, Qi Fan and Sirota, Inna and Ran, Leili and MacDonald, Theresa Y and Beltran, Himisha and Mosquera, Juan-Miguel 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 Chi, Ping and Carver, Brett and Rubin, Mark A and Scher, Howard I and Clevers, Hans and Sawyers, Charles L and Chen, Yu},
  issn         = {1097-4172},
  keyword      = {Culture Techniques,Heterografts,Humans,Male,Neoplasm Metastasis,Organoids,Pharmacology,Prostatic Neoplasms,Tumor Suppressor Proteins,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't,Research Support, U.S. Gov't, Non-P.H.S.},
  language     = {eng},
  month        = {09},
  number       = {1},
  pages        = {176--187},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {Organoid cultures derived from patients with advanced prostate cancer},
  url          = {http://dx.doi.org/10.1016/j.cell.2014.08.016},
  volume       = {159},
  year         = {2014},
}