Organoid cultures derived from patients with advanced prostate cancer Journal Article


Authors: 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.; Sirota, I.; Ran, L.; MacDonald, T. Y.; Beltran, H.; Mosquera, J. M.; Touijer, K. A.; Scardino, P. T.; Laudone, V. P.; Curtis, K. R.; Rathkopf, D. E.; Morris, M. J.; Danila, D. C.; Slovin, S. F.; Solomon, S. B.; Eastham, J. A.; Chi, P.; Carver, B.; Rubin, M. A.; Scher, H. I.; Clevers, H.; Sawyers, C. L.; Chen, Y.
Article 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.
Keywords: clinical article; controlled study; human tissue; gene mutation; gene sequence; human cell; advanced cancer; nonhuman; cancer patient; mouse; dna repair; gene overexpression; animal experiment; animal model; gene function; tumor xenograft; protein p53; prostate cancer; dna; nucleotide sequence; prostate biopsy; fusion gene; gene loss; molecular biology; tumor gene; retinoblastoma protein; circulating tumor cell; spink1 gene; foxa1 gene; pik3r1 gene; human; male; article; chromodomain helicase dna binding protein 1 gene; organ culture; prostate cancer cell line; spop gene; tmprss2 erg fusion gene
Journal Title: Cell
Volume: 159
Issue: 1
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2014-09-25
Start Page: 176
End Page: 187
Language: English
DOI: 10.1016/j.cell.2014.08.016
PROVIDER: scopus
PUBMED: 25201530
PMCID: PMC4237931
DOI/URL:
Notes: Export Date: 3 November 2014 -- Molecular Sequence Numbers: GENBANK: GSE60612; -- Source: Scopus
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MSK Authors
  1. Charles L Sawyers
    153 Sawyers
  2. Vincent Laudone
    59 Laudone
  3. Susan Slovin
    184 Slovin
  4. Michael Morris
    274 Morris
  5. Peter T Scardino
    621 Scardino
  6. Yu Chen
    67 Chen
  7. Abdelkrim Karim Touijer
    190 Touijer
  8. Ping Chi
    44 Chi
  9. Anuradha Gopalan
    273 Gopalan
  10. Vivek Kumar Arora
    10 Arora
  11. Stephen Solomon
    266 Solomon
  12. Dana Elizabeth Rathkopf
    142 Rathkopf
  13. James Eastham
    426 Eastham
  14. Brett Stewart Carver
    109 Carver
  15. Howard Scher
    818 Scher
  16. Daniel C Danila
    82 Danila
  17. Leili Ran
    17 Ran
  18. Zhen Cao
    15 Cao
  19. Inna Sirota
    6 Sirota
  20. Dong Gao
    22 Gao
  21. Ian Vela
    4 Vela
  22. Qi Fan Zhang
    2 Zhang
  23. Kristen   Curtis
    11 Curtis
  24. Wei   Di
    1 Di