Organoid cultures derived from patients with advanced prostate cancer
| Autor: | Himisha Beltran, Howard I. Scher, Eva Undvall, Myriam Kossai, Susan F. Slovin, Juan Miguel Mosquera, Wouter R. Karthaus, James A. Eastham, Wei Di, Michael J. Morris, Sinan Ramazanoglu, Jackline Wanjala, Karim Touijer, Ian Vela, Brett S. Carver, Vincent P. Laudone, Zhen Cao, Charles L. Sawyers, Dong Gao, Leili Ran, Andrea Sboner, Hans Clevers, Daniel C. Danila, Yu Chen, Theresa Y MacDonald, Vivek K. Arora, Luendreo P Barboza, Qi Fan Zhang, Anuradha Gopalan, Dana E. Rathkopf, Ping Chi, Catherine Dowling, Inna Sirota, Kristen Rebecca Curtis, Stephen B. Solomon, Mark A. Rubin, Peter T. Scardino, Phillip J. Iaquinta, John Wongvipat |
|---|---|
| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Rok vydání: | 2014 |
| Předmět: |
Male
Pharmacology Mutation Biochemistry Genetics and Molecular Biology(all) Tumor Suppressor Proteins Cancer Prostatic Neoplasms Chromoplexy SPOP Biology medicine.disease medicine.disease_cause General Biochemistry Genetics and Molecular Biology Organoids Prostate cancer Circulating tumor cell Culture Techniques Immunology Organoid Cancer research medicine Heterografts Humans FOXA1 Neoplasm Metastasis |
| Zdroj: | Cell, 159(1), 176-87. Elsevier B.V. |
| ISSN: | 1097-4172 0092-8674 |
| Popis: | SummaryThe 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|