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47 results on '"Selcuklu, S. Duygu"'

1. Tumor fraction-guided cell-free DNA profiling in metastatic solid tumor patients

Author

Tsui, Dana W. Y., Cheng, Michael L., Shady, Maha, Yang, Julie L., Stephens, Dennis, Won, Helen, Srinivasan, Preethi, Huberman, Kety, Meng, Fanli, Jing, Xiaohong, Patel, Juber, Hasan, Maysun, Johnson, Ian, Gedvilaite, Erika, Houck-Loomis, Brian, Socci, Nicholas D., Selcuklu, S. Duygu, Seshan, Venkatraman E., Zhang, Hongxin, Chakravarty, Debyani, Zehir, Ahmet, Benayed, Ryma, Arcila, Maria, Ladanyi, Marc, Funt, Samuel A., Feldman, Darren R., Li, Bob T., Razavi, Pedram, Rosenberg, Jonathan, Bajorin, Dean, Iyer, Gopa, Abida, Wassim, Scher, Howard I., Rathkopf, Dana, Viale, Agnes, Berger, Michael F., and Solit, David B.

Published
2021
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2. Tumour lineage shapes BRCA-mediated phenotypes

Author

Jonsson, Philip, Bandlamudi, Chaitanya, Cheng, Michael L., Srinivasan, Preethi, Chavan, Shweta S., Friedman, Noah D., Rosen, Ezra Y., Richards, Allison L., Bouvier, Nancy, Selcuklu, S. Duygu, Bielski, Craig M., Abida, Wassim, Mandelker, Diana, Birsoy, Ozge, Zhang, Liying, Zehir, Ahmet, Donoghue, Mark T. A., Baselga, José, Offit, Kenneth, Scher, Howard I., O’Reilly, Eileen M., Stadler, Zsofia K., Schultz, Nikolaus, Socci, Nicholas D., Viale, Agnes, Ladanyi, Marc, Robson, Mark E., Hyman, David M., Berger, Michael F., Solit, David B., and Taylor, Barry S.

Published
2019
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3. Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid

Author

Miller, Alexandra M., Shah, Ronak H., Pentsova, Elena I., Pourmaleki, Maryam, Briggs, Samuel, Distefano, Natalie, Zheng, Youyun, Skakodub, Anna, Mehta, Smrutiben A., Campos, Carl, Hsieh, Wan-Ying, Selcuklu, S. Duygu, Ling, Lilan, Meng, Fanli, Jing, Xiaohong, Samoila, Aliaksandra, Bale, Tejus A., Tsui, Dana W. Y., Grommes, Christian, Viale, Agnes, Souweidane, Mark M., Tabar, Viviane, Brennan, Cameron W., Reiner, Anne S., Rosenblum, Marc, Panageas, Katherine S., DeAngelis, Lisa M., Young, Robert J., Berger, Michael F., and Mellinghoff, Ingo K.

Published
2019
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5. Supplementary Table S2 from Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach

Author

Doe-Tetteh, Seyram A., primary, Camp, Sabrina Y., primary, Reales, Dalicia, primary, Crowdis, Jett, primary, Noronha, Anne Marie, primary, Wolff, Bernadette, primary, Alano, Tina, primary, Galle, Jesse, primary, Selcuklu, S. Duygu, primary, Viale, Agnes, primary, Socci, Nicholas D., primary, Liu, Ying L., primary, Tew, William P., primary, Aghajanian, Carol, primary, Ladanyi, Marc, primary, He, Meng Xiao, primary, AlDubayan, Saud H., primary, Mazor, Roei David, primary, Shpilberg, Ofer, primary, Hershkovitz-Rokah, Oshrat, primary, Riancho, Jose A., primary, Hernandez, Jose L., primary, Gonzalez-Vela, M. Carmen, primary, Buthorn, Justin J., primary, Wilson, Manda, primary, Webber, Amy E., primary, Yabe, Mariko, primary, Petrova-Drus, Kseniya, primary, Rosenblum, Marc, primary, Durham, Benjamin H., primary, Abdel-Wahab, Omar, primary, Berger, Michael F., primary, Donoghue, Mark T.A., primary, Kung, Andrew L., primary, Glade Bender, Julia, primary, Shukla, Neerav N., primary, Funt, Samuel A., primary, Dogan, Ahmet, primary, Soslow, Robert A., primary, Al-Ahmadie, Hikmat, primary, Feldman, Darren R., primary, Van Allen, Eliezer M., primary, Diamond, Eli L., primary, and Solit, David B., primary

Published
2023
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6. Data from Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach

Author

Doe-Tetteh, Seyram A., primary, Camp, Sabrina Y., primary, Reales, Dalicia, primary, Crowdis, Jett, primary, Noronha, Anne Marie, primary, Wolff, Bernadette, primary, Alano, Tina, primary, Galle, Jesse, primary, Selcuklu, S. Duygu, primary, Viale, Agnes, primary, Socci, Nicholas D., primary, Liu, Ying L., primary, Tew, William P., primary, Aghajanian, Carol, primary, Ladanyi, Marc, primary, He, Meng Xiao, primary, AlDubayan, Saud H., primary, Mazor, Roei David, primary, Shpilberg, Ofer, primary, Hershkovitz-Rokah, Oshrat, primary, Riancho, Jose A., primary, Hernandez, Jose L., primary, Gonzalez-Vela, M. Carmen, primary, Buthorn, Justin J., primary, Wilson, Manda, primary, Webber, Amy E., primary, Yabe, Mariko, primary, Petrova-Drus, Kseniya, primary, Rosenblum, Marc, primary, Durham, Benjamin H., primary, Abdel-Wahab, Omar, primary, Berger, Michael F., primary, Donoghue, Mark T.A., primary, Kung, Andrew L., primary, Glade Bender, Julia, primary, Shukla, Neerav N., primary, Funt, Samuel A., primary, Dogan, Ahmet, primary, Soslow, Robert A., primary, Al-Ahmadie, Hikmat, primary, Feldman, Darren R., primary, Van Allen, Eliezer M., primary, Diamond, Eli L., primary, and Solit, David B., primary

Published
2023
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7. Supplementary Figure S1 from Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach

Author

Doe-Tetteh, Seyram A., primary, Camp, Sabrina Y., primary, Reales, Dalicia, primary, Crowdis, Jett, primary, Noronha, Anne Marie, primary, Wolff, Bernadette, primary, Alano, Tina, primary, Galle, Jesse, primary, Selcuklu, S. Duygu, primary, Viale, Agnes, primary, Socci, Nicholas D., primary, Liu, Ying L., primary, Tew, William P., primary, Aghajanian, Carol, primary, Ladanyi, Marc, primary, He, Meng Xiao, primary, AlDubayan, Saud H., primary, Mazor, Roei David, primary, Shpilberg, Ofer, primary, Hershkovitz-Rokah, Oshrat, primary, Riancho, Jose A., primary, Hernandez, Jose L., primary, Gonzalez-Vela, M. Carmen, primary, Buthorn, Justin J., primary, Wilson, Manda, primary, Webber, Amy E., primary, Yabe, Mariko, primary, Petrova-Drus, Kseniya, primary, Rosenblum, Marc, primary, Durham, Benjamin H., primary, Abdel-Wahab, Omar, primary, Berger, Michael F., primary, Donoghue, Mark T.A., primary, Kung, Andrew L., primary, Glade Bender, Julia, primary, Shukla, Neerav N., primary, Funt, Samuel A., primary, Dogan, Ahmet, primary, Soslow, Robert A., primary, Al-Ahmadie, Hikmat, primary, Feldman, Darren R., primary, Van Allen, Eliezer M., primary, Diamond, Eli L., primary, and Solit, David B., primary

Published
2023
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8. Supplementary Figure S2 from Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

Author

Smyth, Lillian M., primary, Piha-Paul, Sarina A., primary, Won, Helen H., primary, Schram, Alison M., primary, Saura, Cristina, primary, Loi, Sherene, primary, Lu, Janice, primary, Shapiro, Geoffrey I., primary, Juric, Dejan, primary, Mayer, Ingrid A., primary, Arteaga, Carlos L., primary, de la Fuente, Macarena I., primary, Brufksy, Adam M., primary, Spanggaard, Iben, primary, Mau-Sørensen, Morten, primary, Arnedos, Monica, primary, Moreno, Victor, primary, Boni, Valentina, primary, Sohn, Joohyuk, primary, Schwartzberg, Lee S., primary, Gonzàlez-Farré, Xavier, primary, Cervantes, Andrés, primary, Bidard, François-Clement, primary, Gorelick, Alexander N., primary, Lanman, Richard B., primary, Nagy, Rebecca J., primary, Ulaner, Gary A., primary, Chandarlapaty, Sarat, primary, Jhaveri, Komal, primary, Gavrila, Elena I., primary, Zimel, Catherine, primary, Selcuklu, S. Duygu, primary, Melcer, Myra, primary, Samoila, Aliaksandra, primary, Cai, Yanyan, primary, Scaltriti, Maurizio, primary, Mann, Grace, primary, Xu, Feng, primary, Eli, Lisa D., primary, Dujka, Melanie, primary, Lalani, Alshad S., primary, Bryce, Richard, primary, Baselga, José, primary, Taylor, Barry S., primary, Solit, David B., primary, Meric-Bernstam, Funda, primary, and Hyman, David M., primary

Published
2023
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9. Data from Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

Author

Smyth, Lillian M., primary, Piha-Paul, Sarina A., primary, Won, Helen H., primary, Schram, Alison M., primary, Saura, Cristina, primary, Loi, Sherene, primary, Lu, Janice, primary, Shapiro, Geoffrey I., primary, Juric, Dejan, primary, Mayer, Ingrid A., primary, Arteaga, Carlos L., primary, de la Fuente, Macarena I., primary, Brufksy, Adam M., primary, Spanggaard, Iben, primary, Mau-Sørensen, Morten, primary, Arnedos, Monica, primary, Moreno, Victor, primary, Boni, Valentina, primary, Sohn, Joohyuk, primary, Schwartzberg, Lee S., primary, Gonzàlez-Farré, Xavier, primary, Cervantes, Andrés, primary, Bidard, François-Clement, primary, Gorelick, Alexander N., primary, Lanman, Richard B., primary, Nagy, Rebecca J., primary, Ulaner, Gary A., primary, Chandarlapaty, Sarat, primary, Jhaveri, Komal, primary, Gavrila, Elena I., primary, Zimel, Catherine, primary, Selcuklu, S. Duygu, primary, Melcer, Myra, primary, Samoila, Aliaksandra, primary, Cai, Yanyan, primary, Scaltriti, Maurizio, primary, Mann, Grace, primary, Xu, Feng, primary, Eli, Lisa D., primary, Dujka, Melanie, primary, Lalani, Alshad S., primary, Bryce, Richard, primary, Baselga, José, primary, Taylor, Barry S., primary, Solit, David B., primary, Meric-Bernstam, Funda, primary, and Hyman, David M., primary

Published
2023
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10. Supplementary Figures from Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition

Author

Harding, James J., primary, Lowery, Maeve A., primary, Shih, Alan H., primary, Schvartzman, Juan M., primary, Hou, Shengqi, primary, Famulare, Christopher, primary, Patel, Minal, primary, Roshal, Mikhail, primary, Do, Richard K., primary, Zehir, Ahmet, primary, You, Daoqi, primary, Selcuklu, S. Duygu, primary, Viale, Agnes, primary, Tallman, Martin S., primary, Hyman, David M., primary, Reznik, Ed, primary, Finley, Lydia W.S., primary, Papaemmanuil, Elli, primary, Tosolini, Alessandra, primary, Frattini, Mark G., primary, MacBeth, Kyle J., primary, Liu, Guowen, primary, Fan, Bin, primary, Choe, Sung, primary, Wu, Bin, primary, Janjigian, Yelena Y., primary, Mellinghoff, Ingo K., primary, Diaz, Luis A., primary, Levine, Ross L., primary, Abou-Alfa, Ghassan K., primary, Stein, Eytan M., primary, and Intlekofer, Andrew M., primary

Published
2023
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11. Supplementary Data from Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

Author

Smyth, Lillian M., primary, Piha-Paul, Sarina A., primary, Won, Helen H., primary, Schram, Alison M., primary, Saura, Cristina, primary, Loi, Sherene, primary, Lu, Janice, primary, Shapiro, Geoffrey I., primary, Juric, Dejan, primary, Mayer, Ingrid A., primary, Arteaga, Carlos L., primary, de la Fuente, Macarena I., primary, Brufksy, Adam M., primary, Spanggaard, Iben, primary, Mau-Sørensen, Morten, primary, Arnedos, Monica, primary, Moreno, Victor, primary, Boni, Valentina, primary, Sohn, Joohyuk, primary, Schwartzberg, Lee S., primary, Gonzàlez-Farré, Xavier, primary, Cervantes, Andrés, primary, Bidard, François-Clement, primary, Gorelick, Alexander N., primary, Lanman, Richard B., primary, Nagy, Rebecca J., primary, Ulaner, Gary A., primary, Chandarlapaty, Sarat, primary, Jhaveri, Komal, primary, Gavrila, Elena I., primary, Zimel, Catherine, primary, Selcuklu, S. Duygu, primary, Melcer, Myra, primary, Samoila, Aliaksandra, primary, Cai, Yanyan, primary, Scaltriti, Maurizio, primary, Mann, Grace, primary, Xu, Feng, primary, Eli, Lisa D., primary, Dujka, Melanie, primary, Lalani, Alshad S., primary, Bryce, Richard, primary, Baselga, José, primary, Taylor, Barry S., primary, Solit, David B., primary, Meric-Bernstam, Funda, primary, and Hyman, David M., primary

Published
2023
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12. Supplementary Methods from Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition

Author

Harding, James J., primary, Lowery, Maeve A., primary, Shih, Alan H., primary, Schvartzman, Juan M., primary, Hou, Shengqi, primary, Famulare, Christopher, primary, Patel, Minal, primary, Roshal, Mikhail, primary, Do, Richard K., primary, Zehir, Ahmet, primary, You, Daoqi, primary, Selcuklu, S. Duygu, primary, Viale, Agnes, primary, Tallman, Martin S., primary, Hyman, David M., primary, Reznik, Ed, primary, Finley, Lydia W.S., primary, Papaemmanuil, Elli, primary, Tosolini, Alessandra, primary, Frattini, Mark G., primary, MacBeth, Kyle J., primary, Liu, Guowen, primary, Fan, Bin, primary, Choe, Sung, primary, Wu, Bin, primary, Janjigian, Yelena Y., primary, Mellinghoff, Ingo K., primary, Diaz, Luis A., primary, Levine, Ross L., primary, Abou-Alfa, Ghassan K., primary, Stein, Eytan M., primary, and Intlekofer, Andrew M., primary

Published
2023
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13. Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach

Author

Doe-Tetteh, Seyram A., primary, Camp, Sabrina Y., additional, Reales, Dalicia, additional, Crowdis, Jett, additional, Noronha, Anne Marie, additional, Wolff, Bernadette, additional, Alano, Tina, additional, Galle, Jesse, additional, Selcuklu, S. Duygu, additional, Viale, Agnes, additional, Socci, Nicholas D., additional, Liu, Ying L., additional, Tew, William P., additional, Aghajanian, Carol, additional, Ladanyi, Marc, additional, He, Meng Xiao, additional, AlDubayan, Saud H., additional, Mazor, Roei David, additional, Shpilberg, Ofer, additional, Hershkovitz-Rokah, Oshrat, additional, Riancho, Jose A., additional, Hernandez, Jose L., additional, Gonzalez-Vela, M. Carmen, additional, Buthorn, Justin J., additional, Wilson, Manda, additional, Webber, Amy E., additional, Yabe, Mariko, additional, Petrova-Drus, Kseniya, additional, Rosenblum, Marc, additional, Durham, Benjamin H., additional, Abdel-Wahab, Omar, additional, Berger, Michael F., additional, Donoghue, Mark T.A., additional, Kung, Andrew L., additional, Glade Bender, Julia, additional, Shukla, Neerav N., additional, Funt, Samuel A., additional, Dogan, Ahmet, additional, Soslow, Robert A., additional, Al-Ahmadie, Hikmat, additional, Feldman, Darren R., additional, Van Allen, Eliezer M., additional, Diamond, Eli L., additional, and Solit, David B., additional

Published
2023
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14. Author Correction: Tumour lineage shapes BRCA-mediated phenotypes

Author

Jonsson, Philip, Bandlamudi, Chaitanya, Cheng, Michael L., Srinivasan, Preethi, Chavan, Shweta S., Friedman, Noah D., Rosen, Ezra Y., Richards, Allison L., Bouvier, Nancy, Selcuklu, S. Duygu, Bielski, Craig M., Abida, Wassim, Mandelker, Diana, Birsoy, Ozge, Zhang, Liying, Zehir, Ahmet, Donoghue, Mark T. A., Baselga, José, Offit, Kenneth, Scher, Howard I., O’Reilly, Eileen M., Stadler, Zsofia K., Schultz, Nikolaus, Socci, Nicholas D., Viale, Agnes, Ladanyi, Marc, Robson, Mark E., Hyman, David M., Berger, Michael F., Solit, David B., and Taylor, Barry S.

Published
2020
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15. Author Correction: HER kinase inhibition in patients with HER2- and HER3-mutant cancers

Author

Hyman, David M., Piha-Paul, Sarina A., Won, Helen, Rodon, Jordi, Saura, Cristina, Shapiro, Geoffrey I., Juric, Dejan, Quinn, David I., Moreno, Victor, Doger, Bernard, Mayer, Ingrid A., Boni, Valentina, Calvo, Emiliano, Loi, Sherene, Lockhart, Albert C., Erinjeri, Joseph P., Scaltriti, Maurizio, Ulaner, Gary A., Patel, Juber, Tang, Jiabin, Beer, Hannah, Selcuklu, S. Duygu, Hanrahan, Aphrothiti J., Bouvier, Nancy, Melcer, Myra, Murali, Rajmohan, Schram, Alison M., Smyth, Lillian M., Jhaveri, Komal, Li, Bob T., Drilon, Alexander, Harding, James J., Iyer, Gopa, Taylor, Barry S., Berger, Michael F., Cutler, Jr, Richard E., Xu, Feng, Butturini, Anna, Eli, Lisa D., Mann, Grace, Farrell, Cynthia, Lalani, Alshad S., Bryce, Richard P., Arteaga, Carlos L., Meric-Bernstam, Funda, Baselga, José, and Solit, David B.

Published
2019
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16. Targeting HER2 mutant advanced biliary tract cancers with neratinib: results from the SUMMIT ‘basket’ trial

Author

Harding, James, primary, Piha-Paul, Sarina, additional, Shah, Ronak, additional, Murphy, Jessica, additional, Cleary, James, additional, Shapiro, Geoffrey, additional, Quinn, David, additional, Braña, Irene, additional, Moreno, Victor, additional, Borad, Mitesh, additional, Loi, Sherene, additional, Spanggaard, Iben, additional, Park, Haeseong, additional, Ford, James, additional, Arnedos, Monica, additional, Stemmer, Salomon, additional, Fouchardiere, Christelle de la, additional, Fountzilas, Christos, additional, Zhang, Jie, additional, DiPrimeo, Daniel, additional, Savin, Casey, additional, Selcuklu, S. Duygu, additional, Berger, Michael, additional, Eli, Lisa, additional, Meric-Bernstam, Funda, additional, Jhaveri, Komal, additional, Solit, David, additional, and Abou-Alfa, Ghassan K, additional

Published
2022
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18. Targeting Aurora B kinase prevents and overcomes resistance to EGFR inhibitors in lung cancer by enhancing BIM- and PUMA-mediated apoptosis

Author

Tanaka, Kosuke, primary, Yu, Helena A., additional, Yang, Shaoyuan, additional, Han, Song, additional, Selcuklu, S. Duygu, additional, Kim, Kwanghee, additional, Ramani, Shriram, additional, Ganesan, Yogesh Tengarai, additional, Moyer, Allison, additional, Sinha, Sonali, additional, Xie, Yuchen, additional, Ishizawa, Kota, additional, Osmanbeyoglu, Hatice U., additional, Lyu, Yang, additional, Roper, Nitin, additional, Guha, Udayan, additional, Rudin, Charles M., additional, Kris, Mark G., additional, Hsieh, James J., additional, and Cheng, Emily H., additional

Published
2021
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19. HER kinase inhibition in patients with HER2- and HER3-mutant cancers

Author

Hyman, David M., Piha-Paul, Sarina A., Won, Helen, Rodon, Jordi, Saura, Cristina, Shapiro, Geoffrey I., Juric, Dejan, Quinn, David I., Moreno, Victor, Doger, Bernard, Mayer, Ingrid A., Boni, Valentina, Calvo, Emiliano, Loi, Sherene, Lockhart, Albert C., Erinjeri, Joseph P., Scaltriti, Maurizio, Ulaner, Gary A., Patel, Juber, Tang, Jiabin, Beer, Hannah, Selcuklu, S. Duygu, Hanrahan, Aphrothiti J., Bouvier, Nancy, Melcer, Myra, Murali, Rajmohan, Schram, Alison M., Smyth, Lillian M., Jhaveri, Komal, Li, Bob T., Drilon, Alexander, Harding, James J., Iyer, Gopa, Taylor, Barry S., Berger, Michael F., Cutler Jr, Richard E., Xu, Feng, Butturini, Anna, Eli, Lisa D., Mann, Grace, Farrell, Cynthia, Lalani, Alshad S., Bryce, Richard P., Arteaga, Carlos L., Meric-Bernstam, Funda, Baselga, Jos, and Solit, David B.

Subjects
Cancer -- Genetic aspects, Phosphotransferases -- Health aspects, Gene mutation -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, basket trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.gov identifier NCT01953926). Efficacy in HER2-mutant cancers varied as a function of both tumour type and mutant allele to a degree not predicted by preclinical models, with the greatest activity seen in breast, cervical and biliary cancers and with tumours that contain kinase domain missense mutations. This study demonstrates how a molecularly driven clinical trial can be used to refine our biological understanding of both characterized and new genomic alterations with potential broad applicability for advancing the paradigm of genome-driven oncology., Author(s): David M. Hyman (corresponding author) [1]; Sarina A. Piha-Paul [2]; Helen Won [1]; Jordi Rodon [3]; Cristina Saura [3]; Geoffrey I. Shapiro [4]; Dejan Juric [5]; David I. Quinn [...]

Published
2018
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20. Additional file 2 of Tumor fraction-guided cell-free DNA profiling in metastatic solid tumor patients

Author

Tsui, Dana W. Y., Cheng, Michael L., Shady, Maha, Yang, Julie L., Stephens, Dennis, Won, Helen, Srinivasan, Preethi, Huberman, Kety, Meng, Fanli, Jing, Xiaohong, Patel, Juber, Hasan, Maysun, Johnson, Ian, Gedvilaite, Erika, Houck-Loomis, Brian, Socci, Nicholas D., Selcuklu, S. Duygu, Seshan, Venkatraman E., Zhang, Hongxin, Chakravarty, Debyani, Zehir, Ahmet, Benayed, Ryma, Arcila, Maria, Ladanyi, Marc, Funt, Samuel A., Feldman, Darren R., Li, Bob T., Razavi, Pedram, Rosenberg, Jonathan, Bajorin, Dean, Iyer, Gopa, Abida, Wassim, Scher, Howard I., Rathkopf, Dana, Viale, Agnes, Berger, Michael F., and Solit, David B.

Abstract

Additional file 2: Fig. S1. Summary of the cell-free DNA (cfDNA) profiling assays and number of samples involved in the study. Fig. S2. Evaluation of the tumor fraction estimate determined by ichorCNA in cfDNA of healthy controls and cancer patients. Fig. S3. Distribution of genome-wide z-scores in patients with and without mutations detected by cfMSK-IPMACT. Fig. S4. Comparison of proportion of tumor mutations detected in plasma with z-scores ≥5 and

Published
2021
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21. Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

Author

Smyth, Lillian M, Piha-Paul, Sarina A, Won, Helen H, Schram, Alison M, Saura, Cristina, Loi, Sherene, Lu, Janice, Shapiro, Geoffrey I, Juric, Dejan, Mayer, Ingrid A, Arteaga, Carlos L, de la Fuente, Macarena I, Brufksy, Adam M, Spanggaard, Iben, Mau-Sørensen, Morten, Arnedos, Monica, Moreno, Victor, Boni, Valentina, Sohn, Joohyuk, Schwartzberg, Lee S, Gonzàlez-Farré, Xavier, Cervantes, Andrés, Bidard, François-Clement, Gorelick, Alexander N, Lanman, Richard B, Nagy, Rebecca J, Ulaner, Gary A, Chandarlapaty, Sarat, Jhaveri, Komal, Gavrila, Elena I, Zimel, Catherine, Selcuklu, S Duygu, Melcer, Myra, Samoila, Aliaksandra, Cai, Yanyan, Scaltriti, Maurizio, Mann, Grace, Xu, Feng, Eli, Lisa D, Dujka, Melanie, Lalani, Alshad S, Bryce, Richard, Baselga, José, Taylor, Barry S, Solit, David B, Meric-Bernstam, Funda, Hyman, David M, Smyth, Lillian M, Piha-Paul, Sarina A, Won, Helen H, Schram, Alison M, Saura, Cristina, Loi, Sherene, Lu, Janice, Shapiro, Geoffrey I, Juric, Dejan, Mayer, Ingrid A, Arteaga, Carlos L, de la Fuente, Macarena I, Brufksy, Adam M, Spanggaard, Iben, Mau-Sørensen, Morten, Arnedos, Monica, Moreno, Victor, Boni, Valentina, Sohn, Joohyuk, Schwartzberg, Lee S, Gonzàlez-Farré, Xavier, Cervantes, Andrés, Bidard, François-Clement, Gorelick, Alexander N, Lanman, Richard B, Nagy, Rebecca J, Ulaner, Gary A, Chandarlapaty, Sarat, Jhaveri, Komal, Gavrila, Elena I, Zimel, Catherine, Selcuklu, S Duygu, Melcer, Myra, Samoila, Aliaksandra, Cai, Yanyan, Scaltriti, Maurizio, Mann, Grace, Xu, Feng, Eli, Lisa D, Dujka, Melanie, Lalani, Alshad S, Bryce, Richard, Baselga, José, Taylor, Barry S, Solit, David B, Meric-Bernstam, Funda, and Hyman, David M

Abstract

HER2 mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with HER2-mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER+ patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating HER2 or HER3 alterations were associated with poor treatment outcome. Similarly, acquisition of multiple HER2-activating events, as well as gatekeeper alterations, were observed at disease progression in a high proportion of patients deriving clinical benefit from neratinib. Collectively, these data define HER2 mutations as a therapeutic target in breast cancer and suggest that coexistence of additional HER signaling alterations may promote both de novo and acquired resistance to neratinib. SIGNIFICANCE: HER2 mutations define a targetable breast cancer subset, although sensitivity to irreversible HER kinase inhibition appears to be modified by the presence of concurrent activating genomic events in the pathway. These findings have implications for potential future combinatorial approaches and broader therapeutic development for this genomically defined subset of breast cancer.This article is highlighted in the In This Issue feature, p. 161.

Published
2020

22. Germ Cell Tumor Molecular Heterogeneity Revealed Through Analysis of Primary and Metastasis Pairs

Author

Cheng, Michael L., primary, Donoghue, Mark T.A., additional, Audenet, François, additional, Wong, Nathan C., additional, Pietzak, Eugene J., additional, Bielski, Craig M., additional, Isharwal, Sumit, additional, Iyer, Gopa, additional, Funt, Samuel, additional, Bagrodia, Aditya, additional, Bajorin, Dean F., additional, Reuter, Victor E., additional, Eng, Jana, additional, Joseph, Gabriella, additional, Bourque, Caitlin, additional, Bromberg, Maria, additional, Ling, Lilan, additional, Selcuklu, S. Duygu, additional, Arcila, Maria E., additional, Tsui, Dana W.Y., additional, Zehir, Ahmet, additional, Viale, Agnes, additional, Berger, Michael F., additional, Bosl, George J., additional, Sheinfeld, Joel, additional, Van Allen, Eliezer, additional, Taylor, Barry S., additional, Al-Ahmadie, Hikmat, additional, Solit, David B., additional, and Feldman, Darren R., additional

Published
2020
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23. Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

Author

Smyth, Lillian M., primary, Piha-Paul, Sarina A., additional, Won, Helen H., additional, Schram, Alison M., additional, Saura, Cristina, additional, Loi, Sherene, additional, Lu, Janice, additional, Shapiro, Geoffrey I., additional, Juric, Dejan, additional, Mayer, Ingrid A., additional, Arteaga, Carlos L., additional, de la Fuente, Macarena I., additional, Brufksy, Adam M., additional, Spanggaard, Iben, additional, Mau-Sørensen, Morten, additional, Arnedos, Monica, additional, Moreno, Victor, additional, Boni, Valentina, additional, Sohn, Joohyuk, additional, Schwartzberg, Lee S., additional, Gonzàlez-Farré, Xavier, additional, Cervantes, Andrés, additional, Bidard, François-Clement, additional, Gorelick, Alexander N., additional, Lanman, Richard B., additional, Nagy, Rebecca J., additional, Ulaner, Gary A., additional, Chandarlapaty, Sarat, additional, Jhaveri, Komal, additional, Gavrila, Elena I., additional, Zimel, Catherine, additional, Selcuklu, S. Duygu, additional, Melcer, Myra, additional, Samoila, Aliaksandra, additional, Cai, Yanyan, additional, Scaltriti, Maurizio, additional, Mann, Grace, additional, Xu, Feng, additional, Eli, Lisa D., additional, Dujka, Melanie, additional, Lalani, Alshad S., additional, Bryce, Richard, additional, Baselga, José, additional, Taylor, Barry S., additional, Solit, David B., additional, Meric-Bernstam, Funda, additional, and Hyman, David M., additional

Published
2020
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24. Phase 2 study of LY3023414 in patients with advanced endometrial cancer harboring activating mutations in the PI3K pathway

Author

Rubinstein, Maria M., primary, Hyman, David M., additional, Caird, Imogen, additional, Won, Helen, additional, Soldan, Krysten, additional, Seier, Kenneth, additional, Iasonos, Alexia, additional, Tew, William P., additional, O’Cearbhaill, Roisin E., additional, Grisham, Rachel N., additional, Hensley, Martee L., additional, Troso‐Sandoval, Tiffany, additional, Sabbatini, Paul, additional, Guillen, Joyce, additional, Selcuklu, S. Duygu, additional, Zimel, Catherine, additional, Torrisi, Jean, additional, Aghajanian, Carol, additional, and Makker, Vicky, additional

Published
2019
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25. Author Correction: Tumour lineage shapes BRCA-mediated phenotypes

Author

Jonsson, Philip, primary, Bandlamudi, Chaitanya, additional, Cheng, Michael L., additional, Srinivasan, Preethi, additional, Chavan, Shweta S., additional, Friedman, Noah D., additional, Rosen, Ezra Y., additional, Richards, Allison L., additional, Bouvier, Nancy, additional, Selcuklu, S. Duygu, additional, Bielski, Craig M., additional, Abida, Wassim, additional, Mandelker, Diana, additional, Birsoy, Ozge, additional, Zhang, Liying, additional, Zehir, Ahmet, additional, Donoghue, Mark T. A., additional, Baselga, José, additional, Offit, Kenneth, additional, Scher, Howard I., additional, O’Reilly, Eileen M., additional, Stadler, Zsofia K., additional, Schultz, Nikolaus, additional, Socci, Nicholas D., additional, Viale, Agnes, additional, Ladanyi, Marc, additional, Robson, Mark E., additional, Hyman, David M., additional, Berger, Michael F., additional, Solit, David B., additional, and Taylor, Barry S., additional

Published
2019
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26. Abstract 1752: BRCA-mediated tumorigenesis is origin and cell-type dependent

Author

Jonsson, Philip, primary, Cheng, Michael L., additional, Bandlamudi, Chaitanya, additional, Srinivasan, Preethi, additional, Chavan, Shweta S., additional, Friedman, Noah D., additional, Rosen, Ezra Y., additional, Richards, Allison L., additional, Bouvier, Nancy, additional, Selcuklu, S. Duygu, additional, Bielski, Craig, additional, Abida, Wassim, additional, Zehir, Ahmet, additional, Schultz, Nikolaus, additional, Donoghue, Mark T., additional, Baselga, Jose, additional, Offit, Kenneth, additional, Ladanyi, Marc, additional, O’Reilly, Eileen M., additional, Scher, Howard I., additional, Stadler, Zsofia K., additional, Robson, Mark E., additional, Hyman, David M., additional, Berger, Michael F., additional, Solit, David B., additional, and Taylor, Barry S., additional

Published
2019
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27. Abstract 929: Paired tumor and cfDNA in patients with HER2-mutant solid tumors treated with neratinib reveals convergence of multiple on-target resistance mechanisms: Results from the SUMMIT "Basket" Trial

Author

Won, Helen H., primary, Selcuklu, S. Duygu, additional, Piha-Paul, Sarina A., additional, Saura, Cristina, additional, Rodon, Jordi, additional, Mayer, Ingrid A., additional, Loi, Sherene, additional, Shapiro, Geoffrey I., additional, Lu, Janice, additional, Brufsky, Adam, additional, Zimel, Catherine, additional, Melcer, Myra, additional, Scaltriti, Maurizio, additional, Eli, Lisa D., additional, Cutler, Richard E., additional, Lalani, Alshad S., additional, Bryce, Richard P., additional, Arteaga, Carlos, additional, Meric-Bernstam, Funda, additional, Berger, Michael F., additional, Solit, David B., additional, Schram, Alison, additional, and Hyman, David M., additional

Published
2019
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28. Non-invasive detection of acquired resistance to FGFR inhibition in patients with cholangiocarcinoma harboring FGFR2 alterations.

Author

Varghese, Anna M., primary, Patel, Juber Ahamad A, additional, Janjigian, Yelena Yuriy, additional, Meng, Fanli, additional, Selcuklu, S Duygu, additional, Zimel, Catherine, additional, Hyman, David Michael, additional, Iyer, Gopa, additional, Houck-Loomis, Brian, additional, Abou-Alfa, Ghassan K., additional, Berger, Michael F., additional, and Lowery, Maeve Aine, additional

Published
2019
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29. Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition

Author

Harding, James J., primary, Lowery, Maeve A., additional, Shih, Alan H., additional, Schvartzman, Juan M., additional, Hou, Shengqi, additional, Famulare, Christopher, additional, Patel, Minal, additional, Roshal, Mikhail, additional, Do, Richard K., additional, Zehir, Ahmet, additional, You, Daoqi, additional, Selcuklu, S. Duygu, additional, Viale, Agnes, additional, Tallman, Martin S., additional, Hyman, David M., additional, Reznik, Ed, additional, Finley, Lydia W.S., additional, Papaemmanuil, Elli, additional, Tosolini, Alessandra, additional, Frattini, Mark G., additional, MacBeth, Kyle J., additional, Liu, Guowen, additional, Fan, Bin, additional, Choe, Sung, additional, Wu, Bin, additional, Janjigian, Yelena Y., additional, Mellinghoff, Ingo K., additional, Diaz, Luis A., additional, Levine, Ross L., additional, Abou-Alfa, Ghassan K., additional, Stein, Eytan M., additional, and Intlekofer, Andrew M., additional

Published
2018
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30. Phase 2 study of LY3023414 in patients with advanced endometrial cancer harboring activating mutations in the PI3K pathway.

Author

Rubinstein, Maria M., Hyman, David M., Caird, Imogen, Won, Helen, Soldan, Krysten, Seier, Kenneth, Iasonos, Alexia, Tew, William P., O'Cearbhaill, Roisin E., Grisham, Rachel N., Hensley, Martee L., Troso‐Sandoval, Tiffany, Sabbatini, Paul, Guillen, Joyce, Selcuklu, S. Duygu, Zimel, Catherine, Torrisi, Jean, Aghajanian, Carol, Makker, Vicky, and Troso-Sandoval, Tiffany

Subjects
ENDOMETRIAL cancer, CARCINOSARCOMAS, PROGRESSION-free survival, CANCER treatment, HYPERGLYCEMIA, PYRIDINE, BIOCHEMISTRY, RESEARCH, GENETIC mutation, CLINICAL trials, PHOSPHOTRANSFERASES, RESEARCH methodology, PHOSPHATASES, EVALUATION research, MEDICAL cooperation, TREATMENT effectiveness, CELLULAR signal transduction, PHENOMENOLOGY, COMPARATIVE studies, ENDOMETRIAL tumors, TRANSFERASES, HYPOPHOSPHATEMIA, RESEARCH funding, QUINOLONE antibacterial agents, PEPTIDES, BLOOD protein disorders
Abstract

Background: PI3K pathway activation is common in endometrial cancer. We evaluated the safety and efficacy of the dual PI3K/mTOR inhibitor, LY3023414, in patients with advanced endometrial cancer harboring activating mutations in the PI3K pathway.Methods: We conducted a single-arm phase 2 study of monotherapy LY3023414. Eligible patients had advanced endometrial cancer of any grade, prior management with 1-4 cytotoxic lines, and PI3K pathway activation prospectively defined as a loss-of-function PTEN alteration or activating alteration in PIK3CA, AKT1, PIK3R1, PIK3R2, or MTOR. The primary objective was best overall response rate (ORR) per RECIST 1.1.Results: Twenty-eight patients were treated; histologies included endometroid (39%), carcinosarcoma (25%), serous (21%), and mixed (14%). Patients were heavily pretreated, with a median of 2 prior cytotoxic lines (range, 1-3). The most common alterations involved PIK3CA (68%), PTEN (43%), and PIK3R1 (32%). In the 25 efficacy-evaluable patients, the ORR was 16% (90% CI, 7%-100%), and the clinical benefit rate was 28% (90% CI, 16%-100%). Four patients had a confirmed partial response, and 2 responses lasted for >9 months. The median progression-free survival and overall survival were 2.5 months (95% CI, 1.2-3.0) and 9.2 months (95% CI, 5.0-15.9), respectively. The most common all-grade treatment-related adverse events were anemia (71%), hyperglycemia (71%), hypoalbuminemia (68%), and hypophosphatemia (61%). No correlation between molecular alterations and response was observed.Conclusion: In patients with heavily pretreated advanced endometrial cancer prospectively selected for tumors with activating PI3K pathway mutations, LY3023414 demonstrated modest single-agent activity and a manageable safety profile. [ABSTRACT FROM AUTHOR]

Published
2020
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31. Isoform switching as a mechanism of acquired resistance to isocitrate dehydrogenase inhibition

Author

Harding, James J., primary, Lowery, Maeve A., additional, Shih, Alan H., additional, Schvartzman, Juan M., additional, Hou, Shengqi, additional, Famulare, Christopher, additional, Patel, Minal, additional, Roshal, Mikhail, additional, Do, Richard K. G., additional, Zehir, Ahmet, additional, You, Daoqi, additional, Selcuklu, S. Duygu, additional, Viale, Agnes, additional, Tallman, Martin S., additional, Hyman, David M., additional, Reznik, Ed, additional, Finley, Lydia W.S., additional, Papaemmanuil, Elli, additional, Tosolini, Alessandra, additional, Frattini, Mark G., additional, MacBeth, Kyle J., additional, Liu, Guowen, additional, Fan, Bin, additional, Choe, Sung, additional, Wu, Bin, additional, Janjigian, Yelena Y., additional, Mellinghoff, Ingo K., additional, Diaz, Luis A., additional, Levine, Ross L., additional, Abou-Alfa, Ghassan K., additional, Stein, Eytan M., additional, and Intlekofer, Andrew M., additional

Published
2018
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32. Abstract 5533: Cell-free DNA sequencing in ERBB2-mutant breast cancer patients treated with neratinib and fulvestrant: Exploratory analysis from the Phase 2 SUMMIT ‘basket' trial

Author

Schram, Alison M., primary, Selcuklu, S. Duygu, additional, Nagy, Rebecca J., additional, Smyth, Lillian M., additional, Eli, Lisa D., additional, Cutler, Richard E., additional, Lalani, Alshad S., additional, Hyman, David M., additional, and Lanman, Richard B., additional

Published
2018
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33. Plasma KRAS as a biomarker for pancreatic ductal adenocarcinoma (PDAC).

Author

Krantz, Benjamin A., primary, Tsui, Dana, additional, Lowery, Maeve Aine, additional, Capanu, Marinela, additional, Yu, Kenneth H., additional, Kelsen, David Paul, additional, Gedvilaite, Erika, additional, Zhang, Liguo, additional, Selcuklu, S Duygu, additional, You, Daoqi, additional, Golia Pernicka, Jennifer S, additional, Do, Richard K. G., additional, Iacobuzio-Donahue, Christine A, additional, and O'Reilly, Eileen Mary, additional

Published
2018
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34. AKT Inhibition in Solid Tumors With AKT1 Mutations

Author

Hyman, David M., primary, Smyth, Lillian M., additional, Donoghue, Mark T.A., additional, Westin, Shannon N., additional, Bedard, Philippe L., additional, Dean, Emma J., additional, Bando, Hideaki, additional, El-Khoueiry, Anthony B., additional, Pérez-Fidalgo, José A., additional, Mita, Alain, additional, Schellens, Jan H.M., additional, Chang, Matthew T., additional, Reichel, Jonathan B., additional, Bouvier, Nancy, additional, Selcuklu, S. Duygu, additional, Soumerai, Tara E., additional, Torrisi, Jean, additional, Erinjeri, Joseph P., additional, Ambrose, Helen, additional, Barrett, J. Carl, additional, Dougherty, Brian, additional, Foxley, Andrew, additional, Lindemann, Justin P.O., additional, McEwen, Robert, additional, Pass, Martin, additional, Schiavon, Gaia, additional, Berger, Michael F., additional, Chandarlapaty, Sarat, additional, Solit, David B., additional, Banerji, Udai, additional, Baselga, José, additional, and Taylor, Barry S., additional

Published
2017
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35. Genomic Biomarkers of a Randomized Trial Comparing First-line Everolimus and Sunitinib in Patients with Metastatic Renal Cell Carcinoma

Author

Hsieh, James J., primary, Chen, David, additional, Wang, Patricia I., additional, Marker, Mahtab, additional, Redzematovic, Almedina, additional, Chen, Ying-Bei, additional, Selcuklu, S. Duygu, additional, Weinhold, Nils, additional, Bouvier, Nancy, additional, Huberman, Kety H., additional, Bhanot, Umesh, additional, Chevinsky, Michael S., additional, Patel, Parul, additional, Pinciroli, Patrizia, additional, Won, Helen H., additional, You, Daoqi, additional, Viale, Agnes, additional, Lee, William, additional, Hakimi, A. Ari, additional, Berger, Michael F., additional, Socci, Nicholas D., additional, Cheng, Emily H., additional, Knox, Jennifer, additional, Voss, Martin H., additional, Voi, Maurizio, additional, and Motzer, Robert J., additional

Published
2017
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37. Phase II Trial and Correlative Genomic Analysis of Everolimus Plus Bevacizumab in Advanced Non–Clear Cell Renal Cell Carcinoma

Author

Voss, Martin H., primary, Molina, Ana M., additional, Chen, Ying-Bei, additional, Woo, Kaitlin M., additional, Chaim, Joshua L., additional, Coskey, Devyn T., additional, Redzematovic, Almedina, additional, Wang, Patricia, additional, Lee, William, additional, Selcuklu, S. Duygu, additional, Lee, Chung-Han, additional, Berger, Michael F., additional, Tickoo, Satish K., additional, Reuter, Victor E., additional, Patil, Sujata, additional, Hsieh, James J., additional, Motzer, Robert J., additional, and Feldman, Darren R., additional

Published
2016
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38. Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid

Author

Pentsova, Elena I., primary, Shah, Ronak H., additional, Tang, Jiabin, additional, Boire, Adrienne, additional, You, Daoqi, additional, Briggs, Samuel, additional, Omuro, Antonio, additional, Lin, Xuling, additional, Fleisher, Martin, additional, Grommes, Christian, additional, Panageas, Katherine S., additional, Meng, Fanli, additional, Selcuklu, S. Duygu, additional, Ogilvie, Shahiba, additional, Distefano, Natalie, additional, Shagabayeva, Larisa, additional, Rosenblum, Marc, additional, DeAngelis, Lisa M., additional, Viale, Agnes, additional, Mellinghoff, Ingo K., additional, and Berger, Michael F., additional

Published
2016
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39. Serial next generation sequencing (NGS) of cell free DNA (cfDNA) and clonal evolution of AKT1 E17K mutant tumors: Analyses from patients (pts) enrolled on a phase I basket study of an AKT inhibitor (AZD5363).

Author

Smyth, Lillian Mary, primary, Reichel, Jonathan B, additional, Tang, Jiabin, additional, Patel, Juber Ahamad A, additional, Meng, Fanli, additional, Selcuklu, S Duygu, additional, You, Daoqi, additional, Samoila, Aliaksandra, additional, Schiavon, Gaia, additional, Li, Bob T., additional, Razavi, Pedram, additional, Piscuoglio, Salvatore, additional, Reis-Filho, Jorge S., additional, Hudis, Clifford A., additional, Baselga, Jose, additional, Solit, David B., additional, Taylor, Barry S., additional, Hyman, David Michael, additional, Berger, Michael F., additional, and Chandarlapaty, Sarat, additional

Published
2016
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40. ALCAM is indirectly modulated by miR-125b in MCF7 cells

Author

Akman, H. Begum, primary, Selcuklu, S. Duygu, additional, Donoghue, Mark T. A., additional, Akhavantabasi, Shiva, additional, Sapmaz, Aysegul, additional, Spillane, Charles, additional, Yakicier, M. Cengiz, additional, and Erson-Bensan, A. Elif, additional

Published
2014
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45. An NTD-Associated Polymorphism in the 3′ UTR of MTHFD1 L can Affect Disease Risk by Altering mi RNA Binding.

Author

Minguzzi, Stefano, Selcuklu, S. Duygu, Spillane, Charles, and Parle‐McDermott, Anne

Abstract

ABSTRACT Maternal folate levels and polymorphisms in folate-related genes are known risk factors for neural tube defects ( NTDs). SNPs in the mitochondrial folate gene MTHFD1L are associated with the risk of NTDs. We investigated whether different alleles of SNP rs7646 in the 3′ UTR of MTHFD1L can be differentially regulated by micro RNAs affecting MTHFD1L expression. We previously reported that miR-9 targets MTHFD1L and now we identify miR-197 as an additional mi RNA regulator. Both of these mi RNAs have predicted binding sites in the MTHFD1L 3′ UTR in the region containing SNP rs7646. We have determined whether the alleles of SNP rs7646 (A/G) and mi RNA expression levels affect mi RNA binding preferences for the MTHFD1L 3′ UTR and consequently MTHFD1L expression. Our results indicate that miR-9 and miR-197 specifically downregulate MTHFD1L levels in HEK293 and MCF-7 cells and that SNPrs7646 significantly affects miR-197 binding affinity to the MTHFD1L 3′ UTR, causing more efficient posttranscriptional gene repression in the presence of the allele that is associated with increased risk of NTDs. These results reveal that the association of SNP rs7646 and NTD risk involves differences in micro RNA regulation and, highlights the importance of genotype-dependent differential micro RNA regulation in relation to human disease risk. [ABSTRACT FROM AUTHOR]

Published
2014
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46. MicroRNA-9 Inhibition of Cell Proliferation and Identification of Novel miR-9 Targets by Transcriptome Profiling in Breast Cancer Cells.

Author

Selcuklu, S. Duygu, Donoghue, Mark T. A., Rehmet, Kristina, de Souza Gomes, Matheus, Fort, Antoine, Kovvuru, Prasad, Muniyappa, Mohan K., Kerin, Michael J., Enright, Anton J., and Spillane, Charles

Subjects
*MICRORNA, *CELL proliferation, *BREAST cancer, *CANCER cells, *APOPTOSIS, *CELL lines
Abstract

Although underexpression of miR-9 in cancer cells is reported in many cancer types, it is currently difficult to classify miR-9 as a tumor suppressor or an oncomir. We demonstrate that miR-9 expression is down-regulated in MCF-7 and MDAMB- 231 breast cancer cells compared with MCF-10-2A normal breast cell line. Increasing miR-9 expression levels in breast cancer cells induced anti-proliferative, anti-invasive, and pro-apoptotic activity. In addition, microarray profiling of the transcriptome of MCF-7 cells overexpressing miR-9 identified six novel direct miR-9 targets (AP3B1, CCNG1, LARP1, MTHFD1L, MTHFD2, and SRPK1). Among these, MTHFD2 was identified as a miR-9 target gene that affects cell proliferation. Knockdown of MTHFD2 mimicked the effect observed when miR-9 was overexpressed by decreasing cell viability and increasing apoptotic activity. Despite variable effects on different cell lines, proliferative and anti-apoptotic activity of MTHFD2 was demonstrated whereby it could escape from miR-9-directed suppression (by overexpression of MTHFD2 with mutated miR-9 binding sites). Furthermore, endogenous expression levels of miR-9 and MTHFD2 displayed inverse expression profiles in primary breast tumor samples compared with normal breast samples; miR-9 was down-regulated, and MTHFD2 was up-regulated. These results indicate anti-proliferative and pro-apoptotic activity of miR-9 and that direct targeting of MTHFD2 can contribute to tumor suppressor-like activity of miR-9 in breast cancer cells. [ABSTRACT FROM AUTHOR]

Published
2012
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47. An NTD-associated polymorphism in the 3' UTR of MTHFD1L can affect disease risk by altering miRNA binding.

Author

Minguzzi S, Selcuklu SD, Spillane C, and Parle-McDermott A

Subjects
Alleles, Aminohydrolases chemistry, Binding Sites, Formate-Tetrahydrofolate Ligase chemistry, Gene Expression Regulation, Genetic Predisposition to Disease, Genetic Variation, Genotype, HEK293 Cells, Humans, MCF-7 Cells, Methylenetetrahydrofolate Dehydrogenase (NADP) chemistry, MicroRNAs chemistry, Models, Molecular, Multienzyme Complexes chemistry, Neural Tube Defects metabolism, Polymorphism, Single Nucleotide, Thermodynamics, 3' Untranslated Regions, Aminohydrolases genetics, Aminohydrolases metabolism, Formate-Tetrahydrofolate Ligase genetics, Formate-Tetrahydrofolate Ligase metabolism, Methylenetetrahydrofolate Dehydrogenase (NADP) genetics, Methylenetetrahydrofolate Dehydrogenase (NADP) metabolism, MicroRNAs metabolism, Multienzyme Complexes genetics, Multienzyme Complexes metabolism, Neural Tube Defects genetics
Abstract

Maternal folate levels and polymorphisms in folate-related genes are known risk factors for neural tube defects (NTDs). SNPs in the mitochondrial folate gene MTHFD1L are associated with the risk of NTDs. We investigated whether different alleles of SNP rs7646 in the 3' UTR of MTHFD1L can be differentially regulated by microRNAs affecting MTHFD1L expression. We previously reported that miR-9 targets MTHFD1L and now we identify miR-197 as an additional miRNA regulator. Both of these miRNAs have predicted binding sites in the MTHFD1L 3' UTR in the region containing SNP rs7646. We have determined whether the alleles of SNP rs7646 (A/G) and miRNA expression levels affect miRNA binding preferences for the MTHFD1L 3' UTR and consequently MTHFD1L expression. Our results indicate that miR-9 and miR-197 specifically downregulate MTHFD1L levels in HEK293 and MCF-7 cells and that SNPrs7646 significantly affects miR-197 binding affinity to the MTHFD1L 3' UTR, causing more efficient posttranscriptional gene repression in the presence of the allele that is associated with increased risk of NTDs. These results reveal that the association of SNP rs7646 and NTD risk involves differences in microRNA regulation and, highlights the importance of genotype-dependent differential microRNA regulation in relation to human disease risk., (© 2013 WILEY PERIODICALS, INC.)

Published
2014
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