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Your search keyword '"Gopalan, Anuradha"' showing total 4 results
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4 results on '"Gopalan, Anuradha"'

1. Regenerative potential of prostate luminal cells revealed by single-cell analysis

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Karthaus, Wouter R, Hofree, Matan, Choi, Danielle, Linton, Eliot L, Turkekul, Mesruh, Bejnood, Alborz, Carver, Brett, Gopalan, Anuradha, Abida, Wassim, Laudone, Vincent, Biton, Moshe, Chaudhary, Ojasvi, Xu, Tianhao, Masilionis, Ignas, Manova, Katia, Mazutis, Linas, Pe’er, Dana, Regev, Aviv, Sawyers, Charles L, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Department of Biology, Karthaus, Wouter R, Hofree, Matan, Choi, Danielle, Linton, Eliot L, Turkekul, Mesruh, Bejnood, Alborz, Carver, Brett, Gopalan, Anuradha, Abida, Wassim, Laudone, Vincent, Biton, Moshe, Chaudhary, Ojasvi, Xu, Tianhao, Masilionis, Ignas, Manova, Katia, Mazutis, Linas, Pe’er, Dana, Regev, Aviv, and Sawyers, Charles L

Abstract

Androgen deprivation is the cornerstone of prostate cancer treatment. It results in involution of the normal gland to ~90% of its original size because of the loss of luminal cells. The prostate regenerates when androgen is restored, a process postulated to involve stem cells. Using single-cel RNA sequencing, we identified a rare luminal population in the mouse prostate that expresses stemlike genes (Sca1 and Psca ) and a large population of differentiated cells (Nkx3.1 , Pbsn ). In organoids and in mice, both populations contribute equally to prostate regeneration, partly through androgen-driven expression of growth factors (Nrg2, Rspo3) by mesenchymal cells acting in a paracrine fashion on luminal cells. Analysis of human prostate tissue revealed similar differentiated and stemlike luminal subpopulations that likewise acquire enhanced regenerative potential after androgen ablation. We propose that prostate regeneration is driven by nearly all persisting luminal cells, not just by rare stem cells. + + + +

Published
2021

2. The Molecular Taxonomy of Primary Prostate Cancer

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Bradley, Robert K, Carmell, Michelle, Carter, Scott, Chin, Lynda, Cibulskis, Kristian, Getz, Gad Asher, Heiman, David, Lander, Eric Steven, Lin, Pei, Loda, Massimo, Meyerson, Matthew L, Park, Peter J, Seidman, Jonathan, Sougnez, Carrie L, Verhaak, Roel, Voet, Douglas, Abeshouse, Adam, Ahn, Jaeil, Akbani, Rehan, Ally, Adrian, Amin, Samirkumar, Andry, Christopher D., Annala, Matti, Aprikian, Armen, Armenia, Joshua, Arora, Arshi, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barbieri, Christopher E., Bauer, Thomas, Benz, Christopher C., Bergeron, Alain, Beroukhim, Rameen, Berrios, Mario, Bivol, Adrian, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., dos Reis, Rodolfo Borges, Boutros, Paul C., Bowen, Jay, Bowlby, Reanne, Boyd, Jeffrey, Breggia, Anne, Brimo, Fadi, Brooks, Denise, Broom, Bradley M., Bryce, Alan H., Bubley, Glenn, Burks, Eric, Butterfield, Yaron S.N., Button, Michael, Canes, David, Carlotti, Carlos G., Carlsen, Rebecca, Carroll, Peter R., Cartun, Richard, Carver, Brett S., Chan, June M., Chang, Matthew T., Chen, Yu, Costello, Anthony J., Cherniack, Andrew D., Chevalier, Simone, Cho, Juok, Chu, Andy, Chuah, Eric, Chudamani, Sudha, Ciriello, Giovanni, Clarke, Amanda, Cooperberg, Matthew R., Corcoran, Niall M., Cowan, Janet, Crain, Daniel, Curley, Erin, David, Kerstin, Demchok, John A., Demichelis, Francesca, Dhalla, Noreen, Dhir, Rajiv, Doueik, Alexandre, Drake, Bettina, Dvinge, Heidi, Dyakova, Natalya, Felau, Ina, Ferguson, Martin L., Frazer, Scott, Freedland, Stephen, Fu, Yao, Bristow, Christopher A., Gao, Jianjiong, Gardner, Johanna, Gastier-Foster, Julie M., Gehlenborg, Nils, Gerken, Mark, Gerstein, Mark B., Godwin, Andrew K., Gopalan, Anuradha, Graefen, Markus, Graim, Kiley, Gribbin, Thomas, Guin, Ranabir, Gupta, Manaswi, Hadjipanayis, Angela, Haider, Syed, Hamel, Lucie, Hayes, D. Neil, Hess, Julian, Hoadley, Katherine A., Holbrook, Andrea H., Holt, Robert A., Holway, Antonia, Hovens, Christopher M., Hoyle, Alan P., Huang, Mei, Hutter, Carolyn M., Ittmann, Michael, Iype, Lisa, Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J.M., Juhl, Hartmut, Kahles, Andre, Kane, Christopher J., Kasaian, Katayoon, Kerger, Michael, Khurana, Ekta, Kim, Jaegil, Klein, Robert J., Kucherlapati, Raju, Lacombe, Louis, Ladanyi, Marc, Lai, Phillip H., Laird, Peter W., Latour, Mathieu, Lawrence, Michael S., Lau, Kevin, LeBien, Tucker, Lee, Darlene, Lee, Semin, Lehmann, Kjong-Van, Leraas, Kristen M., Leshchiner, Ignaty, Leung, Robert, Libertino, John A., Lichtenberg, Tara M., Linehan, W. Marston, Ling, Shiyun, Lippman, Scott M., Liu, Jia, Liu, Wenbin, Lochovsky, Lucas, Logothetis, Christopher, Lolla, Laxmi, Longacre, Teri, Lu, Yiling, Luo, Jianhua, Ma, Yussanne, Mahadeshwar, Harshad S., Mallery, David, Mariamidze, Armaz, Marra, Marco A., Mayo, Michael, McCall, Shannon, McKercher, Ginette, Meng, Shaowu, Mes-Masson, Anne-Marie, Merino, Maria J., Mieczkowski, Piotr A., Mills, Gordon B., Mills Shaw, Kenna R., Minner, Sarah, Moinzadeh, Alireza, Moore, Richard A., Morris, Scott, Morrison, Carl, Mose, Lisle E., Mungall, Andrew J., Murray, Bradley A., Myers, Jerome B., Naresh, Rashi, Nelson, Joel, Nelson, Mark A., Nelson, Peter S., Newton, Yulia, Noble, Michael S., Noushmehr, Houtan, Nykter, Matti, Pantazi, Angeliki, Parfenov, Michael, Parker, Joel S., Paulauskis, Joseph, Penny, Robert, Perou, Charles M., Piche, Alain, Pihl, Todd, Pinto, Peter A., Prandi, Davide, Protopopov, Alexei, Ramirez, Nilsa C., Rao, Arvind, Rathmell, W. Kimryn, Ratsch, Gunnar, Ren, Xiaojia, Reuter, Victor E., Reynolds, Sheila M., Rhie, Suhn K., Rieger-Christ, Kimberly, Roach, Jeffrey, Robertson, A. Gordon, Robinson, Brian, Rubin, Mark A., Saad, Fred, Sadeghi, Sara, Saksena, Gordon, Saller, Charles, Salner, Andrew, Sanchez-Vega, Francisco, Sander, Chris, Sandusky, George, Sauter, Guido, Sboner, Andrea, Scardino, Peter T., Scarlata, Eleonora, Schein, Jacqueline E., Schlomm, Thorsten, Schmidt, Laura S., Schultz, Nikolaus, Schumacher, Steven E., Neder, Luciano, Seth, Sahil, Sharp, Alexis, Shelton, Candace, Shelton, Troy, Shen, Hui, Shen, Ronglai, Sherman, Mark, Sheth, Margi, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Simko, Jeffry, Simon, Ronald, Simons, Janae V., Sipahimalani, Payal, Skelly, Tara, Sofia, Heidi J., Soloway, Matthew G., Song, Xingzhi, Sorcini, Andrea, Stepa, Serghei, Stewart, Chip, Stewart, John, Stuart, Joshua M., Sullivan, Travis B., Sun, Charlie, Sun, Huandong, Tam, Angela, Tan, Donghui, Tang, Jiabin, Tarnuzzer, Roy, Tarvin, Katherine, Taylor, Barry S., Teebagy, Patrick, Tenggara, Imelda, Tetu, Bernard, Tewari, Ashutosh, Thiessen, Nina, Thompson, Timothy, Thorne, Leigh B., Tirapelli, Daniela P., Tomlins, Scott A., Trevisan, Felipe Amstalden, Troncoso, Patricia, True, Lawrence D., Tsourlakis, Maria Christina, Tyekucheva, Svitlana, Van Allen, Eliezer, Van Den Berg, David J., Veluvolu, Umadevi, Vocke, Cathy D., Wan, Yunhu, Wang, Qingguo, Wang, Wenyi, Wang, Zhining, Weinhold, Nils, Weinstein, John N., Weisenberger, Daniel J., Wilkerson, Matthew D., Wise, Lisa, Witte, John, Wu, Chia-Chin, Wu, Junyuan, Wu, Ye, Xu, Andrew W., Yadav, Shalini S., Yang, Liming, Yang, Lixing, Yau, Christina, Ye, Huihui, Yena, Peggy, Zeng, Thomas, Zenklusen, Jean C., Zhang, Hailei, Zhang, Jiashan, Zhang, Wei, Zhong, Yi, Zhu, Kelsey, Zmuda, Erik, Cancer Genome Atlas Research Network, Bradley, Robert K., Meyerson, Matthew L., Park, Peter J., Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Broad Institute of MIT and Harvard, Massachusetts Institute of Technology. Department of Biology, Bradley, Robert K, Carmell, Michelle, Carter, Scott, Chin, Lynda, Cibulskis, Kristian, Getz, Gad Asher, Heiman, David, Lander, Eric Steven, Lin, Pei, Loda, Massimo, Meyerson, Matthew L, Park, Peter J, Seidman, Jonathan, Sougnez, Carrie L, Verhaak, Roel, Voet, Douglas, Abeshouse, Adam, Ahn, Jaeil, Akbani, Rehan, Ally, Adrian, Amin, Samirkumar, Andry, Christopher D., Annala, Matti, Aprikian, Armen, Armenia, Joshua, Arora, Arshi, Auman, J. Todd, Balasundaram, Miruna, Balu, Saianand, Barbieri, Christopher E., Bauer, Thomas, Benz, Christopher C., Bergeron, Alain, Beroukhim, Rameen, Berrios, Mario, Bivol, Adrian, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S., dos Reis, Rodolfo Borges, Boutros, Paul C., Bowen, Jay, Bowlby, Reanne, Boyd, Jeffrey, Breggia, Anne, Brimo, Fadi, Brooks, Denise, Broom, Bradley M., Bryce, Alan H., Bubley, Glenn, Burks, Eric, Butterfield, Yaron S.N., Button, Michael, Canes, David, Carlotti, Carlos G., Carlsen, Rebecca, Carroll, Peter R., Cartun, Richard, Carver, Brett S., Chan, June M., Chang, Matthew T., Chen, Yu, Costello, Anthony J., Cherniack, Andrew D., Chevalier, Simone, Cho, Juok, Chu, Andy, Chuah, Eric, Chudamani, Sudha, Ciriello, Giovanni, Clarke, Amanda, Cooperberg, Matthew R., Corcoran, Niall M., Cowan, Janet, Crain, Daniel, Curley, Erin, David, Kerstin, Demchok, John A., Demichelis, Francesca, Dhalla, Noreen, Dhir, Rajiv, Doueik, Alexandre, Drake, Bettina, Dvinge, Heidi, Dyakova, Natalya, Felau, Ina, Ferguson, Martin L., Frazer, Scott, Freedland, Stephen, Fu, Yao, Bristow, Christopher A., Gao, Jianjiong, Gardner, Johanna, Gastier-Foster, Julie M., Gehlenborg, Nils, Gerken, Mark, Gerstein, Mark B., Godwin, Andrew K., Gopalan, Anuradha, Graefen, Markus, Graim, Kiley, Gribbin, Thomas, Guin, Ranabir, Gupta, Manaswi, Hadjipanayis, Angela, Haider, Syed, Hamel, Lucie, Hayes, D. Neil, Hess, Julian, Hoadley, Katherine A., Holbrook, Andrea H., Holt, Robert A., Holway, Antonia, Hovens, Christopher M., Hoyle, Alan P., Huang, Mei, Hutter, Carolyn M., Ittmann, Michael, Iype, Lisa, Jefferys, Stuart R., Jones, Corbin D., Jones, Steven J.M., Juhl, Hartmut, Kahles, Andre, Kane, Christopher J., Kasaian, Katayoon, Kerger, Michael, Khurana, Ekta, Kim, Jaegil, Klein, Robert J., Kucherlapati, Raju, Lacombe, Louis, Ladanyi, Marc, Lai, Phillip H., Laird, Peter W., Latour, Mathieu, Lawrence, Michael S., Lau, Kevin, LeBien, Tucker, Lee, Darlene, Lee, Semin, Lehmann, Kjong-Van, Leraas, Kristen M., Leshchiner, Ignaty, Leung, Robert, Libertino, John A., Lichtenberg, Tara M., Linehan, W. Marston, Ling, Shiyun, Lippman, Scott M., Liu, Jia, Liu, Wenbin, Lochovsky, Lucas, Logothetis, Christopher, Lolla, Laxmi, Longacre, Teri, Lu, Yiling, Luo, Jianhua, Ma, Yussanne, Mahadeshwar, Harshad S., Mallery, David, Mariamidze, Armaz, Marra, Marco A., Mayo, Michael, McCall, Shannon, McKercher, Ginette, Meng, Shaowu, Mes-Masson, Anne-Marie, Merino, Maria J., Mieczkowski, Piotr A., Mills, Gordon B., Mills Shaw, Kenna R., Minner, Sarah, Moinzadeh, Alireza, Moore, Richard A., Morris, Scott, Morrison, Carl, Mose, Lisle E., Mungall, Andrew J., Murray, Bradley A., Myers, Jerome B., Naresh, Rashi, Nelson, Joel, Nelson, Mark A., Nelson, Peter S., Newton, Yulia, Noble, Michael S., Noushmehr, Houtan, Nykter, Matti, Pantazi, Angeliki, Parfenov, Michael, Parker, Joel S., Paulauskis, Joseph, Penny, Robert, Perou, Charles M., Piche, Alain, Pihl, Todd, Pinto, Peter A., Prandi, Davide, Protopopov, Alexei, Ramirez, Nilsa C., Rao, Arvind, Rathmell, W. Kimryn, Ratsch, Gunnar, Ren, Xiaojia, Reuter, Victor E., Reynolds, Sheila M., Rhie, Suhn K., Rieger-Christ, Kimberly, Roach, Jeffrey, Robertson, A. Gordon, Robinson, Brian, Rubin, Mark A., Saad, Fred, Sadeghi, Sara, Saksena, Gordon, Saller, Charles, Salner, Andrew, Sanchez-Vega, Francisco, Sander, Chris, Sandusky, George, Sauter, Guido, Sboner, Andrea, Scardino, Peter T., Scarlata, Eleonora, Schein, Jacqueline E., Schlomm, Thorsten, Schmidt, Laura S., Schultz, Nikolaus, Schumacher, Steven E., Neder, Luciano, Seth, Sahil, Sharp, Alexis, Shelton, Candace, Shelton, Troy, Shen, Hui, Shen, Ronglai, Sherman, Mark, Sheth, Margi, Shi, Yan, Shih, Juliann, Shmulevich, Ilya, Simko, Jeffry, Simon, Ronald, Simons, Janae V., Sipahimalani, Payal, Skelly, Tara, Sofia, Heidi J., Soloway, Matthew G., Song, Xingzhi, Sorcini, Andrea, Stepa, Serghei, Stewart, Chip, Stewart, John, Stuart, Joshua M., Sullivan, Travis B., Sun, Charlie, Sun, Huandong, Tam, Angela, Tan, Donghui, Tang, Jiabin, Tarnuzzer, Roy, Tarvin, Katherine, Taylor, Barry S., Teebagy, Patrick, Tenggara, Imelda, Tetu, Bernard, Tewari, Ashutosh, Thiessen, Nina, Thompson, Timothy, Thorne, Leigh B., Tirapelli, Daniela P., Tomlins, Scott A., Trevisan, Felipe Amstalden, Troncoso, Patricia, True, Lawrence D., Tsourlakis, Maria Christina, Tyekucheva, Svitlana, Van Allen, Eliezer, Van Den Berg, David J., Veluvolu, Umadevi, Vocke, Cathy D., Wan, Yunhu, Wang, Qingguo, Wang, Wenyi, Wang, Zhining, Weinhold, Nils, Weinstein, John N., Weisenberger, Daniel J., Wilkerson, Matthew D., Wise, Lisa, Witte, John, Wu, Chia-Chin, Wu, Junyuan, Wu, Ye, Xu, Andrew W., Yadav, Shalini S., Yang, Liming, Yang, Lixing, Yau, Christina, Ye, Huihui, Yena, Peggy, Zeng, Thomas, Zenklusen, Jean C., Zhang, Hailei, Zhang, Jiashan, Zhang, Wei, Zhong, Yi, Zhu, Kelsey, Zmuda, Erik, Cancer Genome Atlas Research Network, Bradley, Robert K., Meyerson, Matthew L., and Park, Peter J.

Abstract

There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects., National Institutes of Health (U.S.). (grant 5U24CA143799), National Institutes of Health (U.S.). (grant 5U24CA143835), National Institutes of Health (U.S.). (grant 5U24CA143840), National Institutes of Health (U.S.). (grant 5U24CA143843), National Institutes of Health (U.S.). (grant 5U24CA143845), National Institutes of Health (U.S.). (grant 5U24CA143848), National Institutes of Health (U.S.). (grant 5U24CA143858), National Institutes of Health (U.S.). (grant 5U24CA143866), National Institutes of Health (U.S.). (grant 5U24CA143867), National Institutes of Health (U.S.). (grant 5U24CA143882), National Institutes of Health (U.S.). (grant 5U24CA143883), National Institutes of Health (U.S.). (grant 5U24CA144025), National Institutes of Health (U.S.). (grant U54HG003067), National Institutes of Health (U.S.). (grant U54HG003079), National Institutes of Health (U.S.). (grant U54HG003273), National Institutes of Health (U.S.). (grant P30CA16672)

Published
2017

3. Organoid cultures derived from patients with advanced prostate cancer

Author

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

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.

Published
2014

4. Organoid cultures derived from patients with advanced prostate cancer

Author

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

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.

Published
2014

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