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2. Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models

Author

Zhang, Huiyuan, Du, Yuchen, Qi, Lin, Xiao, Sophie, Braun, Frank K., Kogiso, Mari, Huang, Yulun, Huang, Frank, Abdallah, Aalaa, Suarez, Milagros, Karthick, Sekar, Ahmed, Nabil M., Salsman, Vita S., Baxter, Patricia A., Su, Jack M., Brat, Daniel J., Hellenbeck, Paul L., Teo, Wan-Yee, Patel, Akash J., and Li, Xiao-Nan

Published
2023
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3. Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma

Author

Rusert, Jessica M, Juarez, Edwin F, Brabetz, Sebastian, Jensen, James, Garancher, Alexandra, Chau, Lianne Q, Tacheva-Grigorova, Silvia K, Wahab, Sameerah, Udaka, Yoko T, Finlay, Darren, Seker-Cin, Huriye, Reardon, Brendan, Gröbner, Susanne, Serrano, Jonathan, Ecker, Jonas, Qi, Lin, Kogiso, Mari, Du, Yuchen, Baxter, Patricia A, Henderson, Jacob J, Berens, Michael E, Vuori, Kristiina, Milde, Till, Cho, Yoon-Jae, Li, Xiao-Nan, Olson, James M, Reyes, Iris, Snuderl, Matija, Wong, Terence C, Dimmock, David P, Nahas, Shareef A, Malicki, Denise, Crawford, John R, Levy, Michael L, Van Allen, Eliezer M, Pfister, Stefan M, Tamayo, Pablo, Kool, Marcel, Mesirov, Jill P, and Wechsler-Reya, Robert J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Sciences, Oncology and Carcinogenesis, Brain Disorders, Neurosciences, Pediatric, Orphan Drug, Biotechnology, Genetic Testing, Cancer, Human Genome, Pediatric Research Initiative, Rare Diseases, Brain Cancer, Pediatric Cancer, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Generic health relevance, Good Health and Well Being, Animals, Antineoplastic Agents, Cell Line, Tumor, Cerebellar Neoplasms, Child, Dactinomycin, Gene Expression Regulation, Neoplastic, High-Throughput Screening Assays, Humans, Male, Medulloblastoma, Mice, Inbred NOD, Mutation, Polymorphism, Single Nucleotide, Precision Medicine, Exome Sequencing, Xenograft Model Antitumor Assays, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Medulloblastoma is among the most common malignant brain tumors in children. Recent studies have identified at least four subgroups of the disease that differ in terms of molecular characteristics and patient outcomes. Despite this heterogeneity, most patients with medulloblastoma receive similar therapies, including surgery, radiation, and intensive chemotherapy. Although these treatments prolong survival, many patients still die from the disease and survivors suffer severe long-term side effects from therapy. We hypothesize that each patient with medulloblastoma is sensitive to different therapies and that tailoring therapy based on the molecular and cellular characteristics of patients' tumors will improve outcomes. To test this, we assembled a panel of orthotopic patient-derived xenografts (PDX) and subjected them to DNA sequencing, gene expression profiling, and high-throughput drug screening. Analysis of DNA sequencing revealed that most medulloblastomas do not have actionable mutations that point to effective therapies. In contrast, gene expression and drug response data provided valuable information about potential therapies for every tumor. For example, drug screening demonstrated that actinomycin D, which is used for treatment of sarcoma but rarely for medulloblastoma, was active against PDXs representing Group 3 medulloblastoma, the most aggressive form of the disease. Functional analysis of tumor cells was successfully used in a clinical setting to identify more treatment options than sequencing alone. These studies suggest that it should be possible to move away from a one-size-fits-all approach and begin to treat each patient with therapies that are effective against their specific tumor. SIGNIFICANCE: These findings show that high-throughput drug screening identifies therapies for medulloblastoma that cannot be predicted by genomic or transcriptomic analysis.

Published
2020

4. Epigenetic Alterations of Repeated Relapses in Patient-matched Childhood Ependymomas

Author

Zhao, Sibo, Li, Jia, Zhang, Huiyuan, Qi, Lin, Du, Yuchen, Kogiso, Mari, Braun, Frank K., Xiao, Sophie, Huang, Yulun, Li, Jianfang, Teo, Wan-Yee, Lindsay, Holly, Baxter, Patricia, Su, Jack M. F., Adesina, Adekunle, Laczik, Miklós, Genevini, Paola, Veillard, Anne-Clemence, Schvartzman, Sol, Berguet, Geoffrey, Ding, Shi-Rong, Du, Liping, Stephan, Clifford, Yang, Jianhua, Davies, Peter J. A., Lu, Xinyan, Chintagumpala, Murali, Parsons, Donald William, Perlaky, Laszlo, Xia, Yun-Fei, Man, Tsz-Kwong, Huang, Yun, Sun, Deqiang, and Li, Xiao-Nan

Published
2022
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5. Publisher Correction: Epigenetic alterations of repeated relapses in patient-matched childhood ependymomas

Author

Zhao, Sibo, Li, Jia, Zhang, Huiyuan, Qi, Lin, Du, Yuchen, Kogiso, Mari, Braun, Frank K., Xiao, Sophie, Huang, Yulun, Li, Jianfang, Teo, Wan-Yee, Lindsay, Holly, Baxter, Patricia, Su, Jack M. F., Adesina, Adekunle, Laczik, Miklós, Genevini, Paola, Veillard, Anne-Clemence, Schvartzman, Sol, Berguet, Geoffrey, Ding, Shi-Rong, Du, Liping, Stephan, Clifford, Yang, Jianhua, Davies, Peter J. A., Lu, Xinyan, Chintagumpala, Murali, Parsons, Donald William, Perlaky, Laszlo, Xia, Yun-Fei, Man, Tsz-Kwong, Huang, Yun, Sun, Deqiang, and Li, Xiao-Nan

Published
2022
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7. Direct Implantation of Patient Brain Tumor Cells into Matching Locations in Mouse Brains for Patient-Derived Orthotopic Xenograft Model Development

Author

Qi, Lin, primary, Baxter, Patricia, additional, Kogiso, Mari, additional, Zhang, Huiyuan, additional, Braun, Frank K., additional, Lindsay, Holly, additional, Zhao, Sibo, additional, Xiao, Sophie, additional, Abdallah, Aalaa Sanad, additional, Suarez, Milagros, additional, Huang, Zilu, additional, Teo, Wan Yee, additional, Yu, Litian, additional, Zhao, Xiumei, additional, Liu, Zhigang, additional, Huang, Yulun, additional, Su, Jack M., additional, Man, Tsz-Kwong, additional, Lau, Ching C., additional, Perlaky, Laszlo, additional, Du, Yuchen, additional, and Li, Xiao-Nan, additional

Published
2024
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9. HDAC and PI3K Antagonists Cooperate to Inhibit Growth of MYC-Driven Medulloblastoma

Author

Pei, Yanxin, Liu, Kun-Wei, Wang, Jun, Garancher, Alexandra, Tao, Ran, Esparza, Lourdes A, Maier, Donna L, Udaka, Yoko T, Murad, Najiba, Morrissy, Sorana, Seker-Cin, Huriye, Brabetz, Sebastian, Qi, Lin, Kogiso, Mari, Schubert, Simone, Olson, James M, Cho, Yoon-Jae, Li, Xiao-Nan, Crawford, John R, Levy, Michael L, Kool, Marcel, Pfister, Stefan M, Taylor, Michael D, and Wechsler-Reya, Robert J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Biotechnology, Rare Diseases, Neurosciences, Pediatric Cancer, Brain Cancer, Pediatric, Brain Disorders, Pediatric Research Initiative, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Animals, Cell Proliferation, Disease Models, Animal, Forkhead Transcription Factors, Genes, Tumor Suppressor, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Medulloblastoma, Mice, Mice, Inbred C57BL, Phosphoinositide-3 Kinase Inhibitors, Proto-Oncogene Proteins c-myc, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

Medulloblastoma (MB) is a highly malignant pediatric brain tumor. Despite aggressive therapy, many patients succumb to the disease, and survivors experience severe side effects from treatment. MYC-driven MB has a particularly poor prognosis and would greatly benefit from more effective therapies. We used an animal model of MYC-driven MB to screen for drugs that decrease viability of tumor cells. Among the most effective compounds were histone deacetylase inhibitors (HDACIs). HDACIs potently inhibit survival of MYC-driven MB cells in vitro, in part by inducing expression of the FOXO1 tumor suppressor gene. HDACIs also synergize with phosphatidylinositol 3-kinase inhibitors to inhibit tumor growth in vivo. These studies identify an effective combination therapy for the most aggressive form of MB.

Published
2016

10. RETRACTED ARTICLE: Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma

Author

Garancher, Alexandra, Suzuki, Hiromichi, Haricharan, Svasti, Chau, Lianne Q., Masihi, Meher Beigi, Rusert, Jessica M., Norris, Paula S., Carrette, Florent, Romero, Megan M., Morrissy, Sorana A., Skowron, Patryk, Cavalli, Florence M. G., Farooq, Hamza, Ramaswamy, Vijay, Jones, Steven J. M., Moore, Richard A., Mungall, Andrew J., Ma, Yussanne, Thiessen, Nina, Li, Yisu, Morcavallo, Alaide, Qi, Lin, Kogiso, Mari, Du, Yuchen, Baxter, Patricia, Henderson, Jacob J., Crawford, John R., Levy, Michael L., Olson, James M., Cho, Yoon-Jae, Deshpande, Aniruddha J., Li, Xiao-Nan, Chesler, Louis, Marra, Marco A., Wajant, Harald, Becher, Oren J., Bradley, Linda M., Ware, Carl F., Taylor, Michael D., and Wechsler-Reya, Robert J.

Published
2020
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12. Retraction Note: Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma

Author

Garancher, Alexandra, Suzuki, Hiromichi, Haricharan, Svasti, Chau, Lianne Q., Masihi, Meher Beigi, Rusert, Jessica M., Norris, Paula S., Carrette, Florent, Romero, Megan M., Morrissy, Sorana A., Skowron, Patryk, Cavalli, Florence M. G., Farooq, Hamza, Ramaswamy, Vijay, Jones, Steven J. M., Moore, Richard A., Mungall, Andrew J., Ma, Yussanne, Thiessen, Nina, Li, Yisu, Morcavallo, Alaide, Qi, Lin, Kogiso, Mari, Du, Yuchen, Baxter, Patricia, Henderson, Jacob J., Crawford, John R., Levy, Michael L., Olson, James M., Cho, Yoon-Jae, Deshpande, Aniruddha J., Li, Xiao-Nan, Chesler, Louis, Marra, Marco A., Wajant, Harald, Becher, Oren J., Bradley, Linda M., Ware, Carl F., Taylor, Michael D., and Wechsler-Reya, Robert J.

Published
2022
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13. Supplementary Figure from Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models

Author

Li, Fuyang, primary, Bondra, Kathryn M., primary, Ghilu, Samson, primary, Studebaker, Adam, primary, Liu, Qianqian, primary, Michalek, Joel E., primary, Kogiso, Mari, primary, Li, Xiao-Nan, primary, Kalapurakal, John A., primary, James, C. David, primary, Burma, Sandeep, primary, Kurmasheva, Raushan T., primary, and Houghton, Peter J., primary

Published
2023
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14. Supplementary Tables from Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma

Author

Rusert, Jessica M., primary, Juarez, Edwin F., primary, Brabetz, Sebastian, primary, Jensen, James, primary, Garancher, Alexandra, primary, Chau, Lianne Q., primary, Tacheva-Grigorova, Silvia K., primary, Wahab, Sameerah, primary, Udaka, Yoko T., primary, Finlay, Darren, primary, Seker-Cin, Huriye, primary, Reardon, Brendan, primary, Gröbner, Susanne, primary, Serrano, Jonathan, primary, Ecker, Jonas, primary, Qi, Lin, primary, Kogiso, Mari, primary, Du, Yuchen, primary, Baxter, Patricia A., primary, Henderson, Jacob J., primary, Berens, Michael E., primary, Vuori, Kristiina, primary, Milde, Till, primary, Cho, Yoon-Jae, primary, Li, Xiao-Nan, primary, Olson, James M., primary, Reyes, Iris, primary, Snuderl, Matija, primary, Wong, Terence C., primary, Dimmock, David P., primary, Nahas, Shareef A., primary, Malicki, Denise, primary, Crawford, John R., primary, Levy, Michael L., primary, Van Allen, Eliezer M., primary, Pfister, Stefan M., primary, Tamayo, Pablo, primary, Kool, Marcel, primary, Mesirov, Jill P., primary, and Wechsler-Reya, Robert J., primary

Published
2023
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15. Supplementary Data from Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models

Author

Li, Fuyang, primary, Bondra, Kathryn M., primary, Ghilu, Samson, primary, Studebaker, Adam, primary, Liu, Qianqian, primary, Michalek, Joel E., primary, Kogiso, Mari, primary, Li, Xiao-Nan, primary, Kalapurakal, John A., primary, James, C. David, primary, Burma, Sandeep, primary, Kurmasheva, Raushan T., primary, and Houghton, Peter J., primary

Published
2023
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16. Supplementary Figure S1-S3 from Concurrent Inhibition of Neurosphere and Monolayer Cells of Pediatric Glioblastoma by Aurora A Inhibitor MLN8237 Predicted Survival Extension in PDOX Models

Author

Kogiso, Mari, primary, Qi, Lin, primary, Braun, Frank K., primary, Injac, Sarah G., primary, Zhang, Linna, primary, Du, Yuchen, primary, Zhang, Huiyuan, primary, Lin, Frank Y., primary, Zhao, Sibo, primary, Lindsay, Holly, primary, Su, Jack M., primary, Baxter, Patricia A., primary, Adesina, Adekunle M., primary, Liao, Debra, primary, Qian, Mark G., primary, Berg, Stacey, primary, Muscal, Jodi A., primary, and Li, Xiao-Nan, primary

Published
2023
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17. Supplementary Figures and Legends from Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma

Author

Rusert, Jessica M., primary, Juarez, Edwin F., primary, Brabetz, Sebastian, primary, Jensen, James, primary, Garancher, Alexandra, primary, Chau, Lianne Q., primary, Tacheva-Grigorova, Silvia K., primary, Wahab, Sameerah, primary, Udaka, Yoko T., primary, Finlay, Darren, primary, Seker-Cin, Huriye, primary, Reardon, Brendan, primary, Gröbner, Susanne, primary, Serrano, Jonathan, primary, Ecker, Jonas, primary, Qi, Lin, primary, Kogiso, Mari, primary, Du, Yuchen, primary, Baxter, Patricia A., primary, Henderson, Jacob J., primary, Berens, Michael E., primary, Vuori, Kristiina, primary, Milde, Till, primary, Cho, Yoon-Jae, primary, Li, Xiao-Nan, primary, Olson, James M., primary, Reyes, Iris, primary, Snuderl, Matija, primary, Wong, Terence C., primary, Dimmock, David P., primary, Nahas, Shareef A., primary, Malicki, Denise, primary, Crawford, John R., primary, Levy, Michael L., primary, Van Allen, Eliezer M., primary, Pfister, Stefan M., primary, Tamayo, Pablo, primary, Kool, Marcel, primary, Mesirov, Jill P., primary, and Wechsler-Reya, Robert J., primary

Published
2023
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18. Supplementary Table from Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models

Author

Li, Fuyang, primary, Bondra, Kathryn M., primary, Ghilu, Samson, primary, Studebaker, Adam, primary, Liu, Qianqian, primary, Michalek, Joel E., primary, Kogiso, Mari, primary, Li, Xiao-Nan, primary, Kalapurakal, John A., primary, James, C. David, primary, Burma, Sandeep, primary, Kurmasheva, Raushan T., primary, and Houghton, Peter J., primary

Published
2023
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19. Data from Functional Precision Medicine Identifies New Therapeutic Candidates for Medulloblastoma

Author

Rusert, Jessica M., primary, Juarez, Edwin F., primary, Brabetz, Sebastian, primary, Jensen, James, primary, Garancher, Alexandra, primary, Chau, Lianne Q., primary, Tacheva-Grigorova, Silvia K., primary, Wahab, Sameerah, primary, Udaka, Yoko T., primary, Finlay, Darren, primary, Seker-Cin, Huriye, primary, Reardon, Brendan, primary, Gröbner, Susanne, primary, Serrano, Jonathan, primary, Ecker, Jonas, primary, Qi, Lin, primary, Kogiso, Mari, primary, Du, Yuchen, primary, Baxter, Patricia A., primary, Henderson, Jacob J., primary, Berens, Michael E., primary, Vuori, Kristiina, primary, Milde, Till, primary, Cho, Yoon-Jae, primary, Li, Xiao-Nan, primary, Olson, James M., primary, Reyes, Iris, primary, Snuderl, Matija, primary, Wong, Terence C., primary, Dimmock, David P., primary, Nahas, Shareef A., primary, Malicki, Denise, primary, Crawford, John R., primary, Levy, Michael L., primary, Van Allen, Eliezer M., primary, Pfister, Stefan M., primary, Tamayo, Pablo, primary, Kool, Marcel, primary, Mesirov, Jill P., primary, and Wechsler-Reya, Robert J., primary

Published
2023
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20. EXTH-56. TARGETING GBM WITH AN ONCOLYTIC PICORNAVIRUS SVV-001 ALONE AND IN COMBINATION WITH FRACTIONATED RADIATION IN A NOVEL PANEL OF ORTHOTOPIC PDX MODELS

Author

Zhang, Huiyuan, primary, Du, Yuchen, additional, Qi, Lin, additional, Xiao, Sophie, additional, Braun, Frank K, additional, Kogiso, Mari, additional, Abdallah, Aalaa, additional, Baxter, Patricia A, additional, Su, Jack M, additional, Brat, Daniel, additional, Hallenbeck, Paul L, additional, Teo, Wan-Yee, additional, Patel, Akash, additional, and Li, Xiao-Nan, additional

Published
2022
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21. EPCO-39. ADAPTIVE CONVERGENCE OF METHYLOMES REVEALS EPIGENETIC DRIVERS AND BOOSTERS OF REPEATED RELAPSES IN PATIENT-MATCHED CHILDHOOD EPENDYMOMAS AND IDENTIFIES TARGETS FOR ANTI-RECURRENCE THERAPIES

Author

Zhao, Sibo, primary, Li, Jia Li, additional, Zhang, Huiyuan, additional, Qi, Lin, additional, Du, Yuchen, additional, Kogiso, Mari, additional, Braun, Frank K, additional, Teo, Wan-Yee, additional, Lindsay, Holly, additional, Baxter, Patricia A, additional, Su, Jack M, additional, Adesina, Adekunle, additional, Xiao, Sophie, additional, Stephan, Clifford, additional, Goldman, Stewart G, additional, Davies, Peter J A, additional, Man, Tsz-Kwong, additional, Huang, Yun, additional, Song, Yongcheng, additional, Sun, Deqiang, additional, and Li, Xiao-Nan, additional

Published
2022
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23. Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models

Author

Li, Fuyang, primary, Bondra, Kathryn M., additional, Ghilu, Samson, additional, Studebaker, Adam, additional, Liu, Qianqian, additional, Michalek, Joel E., additional, Kogiso, Mari, additional, Li, Xiao-Nan, additional, Kalapurakal, John A., additional, James, C. David, additional, Burma, Sandeep, additional, Kurmasheva, Raushan T., additional, and Houghton, Peter J., additional

Published
2022
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24. MODL-29. Molecular Landscape of a comprehensive panel of pediatric brain cancer Patient-derived orthotopic xenograft (PDOX) models inform unique targets for drug responsiveness

Author

Braun, Frank K, primary, Brabetz, Sebastian, additional, Qi, Lin, additional, Du, Yuchen, additional, Kogiso, Mari, additional, Zhang, Hui Yuan, additional, Linday, Holly, additional, Teo, Wanyee, additional, Baxter, Patricia, additional, Su, Jack M F, additional, Adekunle, Adesina, additional, Goeun, Bae, additional, Powell, Reid T, additional, Parsons, Donald W, additional, Chintagumpala, Murali, additional, Stephan, Clifford C, additional, Pfister, Stefan, additional, Lau, Ching C, additional, Kool, Marcel, additional, and Li, Xiao-Nan, additional

Published
2022
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25. EPEN-02. Adaptive Convergence of Methylomes Reveals Epigenetic Drivers and Boosters of Repeated Relapses in Patient-matched Childhood Ependymomas and Identifies Targets for Anti-Recurrence Therapies

Author

Zhao, Sibo, primary, Li, Jia, additional, Zhang, Huiyuan, additional, Qi, Lin, additional, Du, Yuchen, additional, Kogiso, Mari, additional, Braun, Frank K, additional, Huang, Yulun, additional, Teo, Wan-Yee, additional, Baxter, Patricia, additional, Adesina, Adekunle, additional, Song, Yongcheng, additional, Sun, Deqiang, additional, and Li, Xiao-Nan, additional

Published
2022
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27. Synergistic anti-tumor efficacy of mutant isocitrate dehydrogenase 1 inhibitor SYC-435 with standard therapy in patient-derived xenograft mouse models of glioma

Author

Kogiso, Mari, primary, Qi, Lin, additional, Du, Yuchen, additional, Braun, Frank K., additional, Zhang, Huiyuan, additional, Huang, L. Frank, additional, Guo, Lei, additional, Huang, Yulun, additional, Teo, Wan-Yee, additional, Lindsay, Holly, additional, Zhao, Sibo, additional, Injac, Sarah G., additional, Liu, Zhen, additional, Mehta, Vidya, additional, Tran, Diep, additional, Li, Feng, additional, Baxter, Patricia A., additional, Su, Jack M., additional, Perlaky, Laszlo, additional, Parsons, D. Williams, additional, Chintagumpala, Murali, additional, Adesina, Adekunle, additional, Song, Yongcheng, additional, and Li, Xiao-Nan, additional

Published
2022
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28. Retraction Note: Tumor necrosis factor overcomes immune evasion in p53-mutant medulloblastoma

Author

Garancher, Alexandra, primary, Suzuki, Hiromichi, additional, Haricharan, Svasti, additional, Chau, Lianne Q., additional, Masihi, Meher Beigi, additional, Rusert, Jessica M., additional, Norris, Paula S., additional, Carrette, Florent, additional, Romero, Megan M., additional, Morrissy, Sorana A., additional, Skowron, Patryk, additional, Cavalli, Florence M. G., additional, Farooq, Hamza, additional, Ramaswamy, Vijay, additional, Jones, Steven J. M., additional, Moore, Richard A., additional, Mungall, Andrew J., additional, Ma, Yussanne, additional, Thiessen, Nina, additional, Li, Yisu, additional, Morcavallo, Alaide, additional, Qi, Lin, additional, Kogiso, Mari, additional, Du, Yuchen, additional, Baxter, Patricia, additional, Henderson, Jacob J., additional, Crawford, John R., additional, Levy, Michael L., additional, Olson, James M., additional, Cho, Yoon-Jae, additional, Deshpande, Aniruddha J., additional, Li, Xiao-Nan, additional, Chesler, Louis, additional, Marra, Marco A., additional, Wajant, Harald, additional, Becher, Oren J., additional, Bradley, Linda M., additional, Ware, Carl F., additional, Taylor, Michael D., additional, and Wechsler-Reya, Robert J., additional

Published
2021
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29. Adaptive Convergence of Methylomes Reveals Epigenetic Drivers and Boosters of Repeated Relapses in Patient-matched Childhood Ependymomas and Identifies Targets for Anti-Recurrence Therapies

Author

Yuanda Hua, Deqiang Sun, Stewart Goldman, Lin Qi, Frank K. Braun, Sibo Zhao, Murali Chintagumpala, Jack Su, Adekunle M. Adesina, Paola Genevini, Xiao-Nan Li, Shirong Ding, Holly Lindsay, Sophie Xiao, Yun-Fei Xia, Yulun Huang, Jia Li, Jianfan Li, Yun Huang, Donald W. Parsons, Laszlo Perlaky, Miklos Miklos, Kogiso Mari, Huiyuan Zhang, Clifford Stephan, Peter F. Davies, Jianhua Yang, Anne-Clémence Veillard, Yuchen Du, Sol Schvartzman, Yongcheng Song, Tsz Kwong Man, Patricia Baxter, and Wan-Yee Teo

Subjects
Oncology, medicine.medical_specialty, business.industry, Internal medicine, medicine, In patient, Childhood ependymoma, Convergence (relationship), Epigenetics, business
Abstract

Ependymoma (EPN) is the third most common brain tumor in children and frequently recurs. Here, we report an integrated longitudinal analysis of epigenetic, genetic and tumorigenic changes in 30 patient-matched repeated relapses obtained from 10 pediatric patients to understand the mechanism of recurrences. Genome-wide DNA methylation analysis revealed stable molecular subtypes and convergent epigenetic reprogramming during serial relapses of the 5 RELA and 5 PFA EPNs that paralleled with elevated patient-derived orthotopic xenograft (PDOX) (13/27) formation in the late relapses. Differentially methylated CpGs (DMCs) preexisted in the primary tumors and persisted in the relapses (driver DMCs) were detected, ranging from 51 hypo-methylated in RELA to 148 hyper-methylated DMCs in PFA tumors; while newly acquired DMCs sustained in all the relapses but was absent in the primary tumors (booster DMCs) ranged from 38- 323 hyper-methylated DMCs in RELA and PFA EPNs, respectively. Integrated analysis of these DMC associated DNA methylation regions (DMRs) and RNAseq in both patient and PDOX tumors identified a small fraction of the differentially expressed genes (4.6±4.4% in RELA and 4.5±1.1% in PFA) as regulated by driver DMRs (e.g., up-regulated CACNA1H, SLC12A7, RARA in RELA and HSPB8, GMPR, ITGB4 in PFA) and booster DMRs (including the sole upregulated PLEKHG1 in RELA and NOTCH, EPHA2, SUFU, FOXJ1 in PFA tumors). Most these genes were novel to EPN relapses. Seven DMCs in RELA and 22 in PFA tumors were also identified as potential relapse predictors. Finally, integrating DNA methylation with histone modification identified LSD1 as a relapse driver gene. Combined treatment of a novel inhibitor SYC-836 with radiation significantly prolonged survival times in two PDOX models of recurrent PFA. This high-resolution epigenetic and genetic roadmap of EPN relapse and our 13 new PDOX models should significantly facilitate biological and preclinical studies of pediatric EPN recurrences.

Published
2021

30. Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion

Author

Huang, Yulun, primary, Qi, Lin, additional, Kogiso, Mari, additional, Du, Yuchen, additional, Braun, Frank K., additional, Zhang, Huiyuan, additional, Huang, L. Frank, additional, Xiao, Sophie, additional, Teo, Wan‐Yee, additional, Lindsay, Holly, additional, Zhao, Sibo, additional, Baxter, Patricia, additional, Su, Jack M. F., additional, Adesina, Adekunle, additional, Yang, Jianhua, additional, Brabetz, Sebastian, additional, Kool, Marcel, additional, Pfister, Stefan M., additional, Chintagumpala, Murali, additional, Perlaky, Laszlo, additional, Wang, Zhong, additional, Zhou, Youxin, additional, Man, Tsz‐Kwong, additional, and Li, Xiao‐Nan, additional

Published
2021
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32. Corrigendum to “Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors” [Cancer Lett. 493 (2020) 197–206]

Author

Qi, Lin, primary, Kogiso, Mari, additional, Du, Yuchen, additional, Zhang, Huiyuan, additional, Braun, Frank K., additional, Huang, Yulun, additional, Teo, Wan-Yee, additional, Lindsay, Holly, additional, Zhao, Sibo, additional, Baxter, Patricia, additional, Zhao, Xiumei, additional, Yu, Litian, additional, Liu, Zhigang, additional, Zhang, Xingding, additional, Su, Jack, additional, Adesina, Adekunle, additional, Yang, Jianhua, additional, Chintagumpala, Murali, additional, Perlaky, Laszlo, additional, Tsz-Kwong Man, Chris, additional, Lau, Ching C., additional, and Li, Xiao-Nan, additional

Published
2021
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33. MBRS-17. EXAMINING THE ROLE OF LHX9 IN GROUP 3 MEDULLOBLASTOMA

Author

Injac, Sarah, primary, Huang, L Frank, additional, Mack, Stephen, additional, Braun, Frank, additional, Du, Yuchen, additional, Kogiso, Mari, additional, Lindsay, Holly, additional, Parsons, D William, additional, Zhao, Hong, additional, Lau, Ching C, additional, Wong, Stephen T C, additional, and Li, Xiao-nan, additional

Published
2020
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34. EPEN-46. DNA METHYLATION LANDSCAPE OF RECURRENT PEDIATRIC EPENDYMOMA IDENTIFIES KEY DRIVER EVENTS

Author

Zhao, Sibo, primary, Li, Jia, additional, Zhang, Huiyuan, additional, Qi, Lin, additional, Du, Yuchen, additional, Kogiso, Mari, additional, Braun, Frank, additional, Lindsay, Holly, additional, Genevini, Paola, additional, Veillard, Anne-Clemence, additional, Schvartzman, Sol, additional, Laczik, Miklos, additional, Berguet, Geoffrey, additional, Adesina, Adekunle, additional, Stephan, Clifford, additional, Chintagumpala, Murali, additional, Parsons, Williams, additional, Perlaky, Laszlo, additional, Song, Yongcheng, additional, Sun, Deqiang, additional, and Li, Xiao-Nan, additional

Published
2020
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37. Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors

Author

Qi, Lin, primary, Kogiso, Mari, additional, Du, Yuchen, additional, Zhang, Huiyuan, additional, Braun, Frank K., additional, Huang, Yulun, additional, Teo, Wan-Yee, additional, Lindsay, Holly, additional, Zhao, Sibo, additional, Baxter, Patricia, additional, Zhao, Xiumei, additional, Yu, Litian, additional, Liu, Zhigang, additional, Zhang, Xingding, additional, Su, Jack MF., additional, Adesina, Adekunle, additional, Yang, Jianhua, additional, Chintagumpala, Murali, additional, Perlaky, Laszlo, additional, Tsz-Kwong Man, Chris, additional, Lau, Ching C., additional, and Li, Xiao-Nan, additional

Published
2020
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38. Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models of Primary and Recurrent Meningioma

Author

Zhang, Huiyuan, primary, Qi, Lin, additional, Du, Yuchen, additional, Huang, L. Frank, additional, Braun, Frank K., additional, Kogiso, Mari, additional, Zhao, Yanling, additional, Li, Can, additional, Lindsay, Holly, additional, Zhao, Sibo, additional, Injac, Sarah G., additional, Baxter, Patricia A., additional, Su, Jack M., additional, Stephan, Clifford, additional, Keller, Charles, additional, Heck, Kent A., additional, Harmanci, Akdes, additional, Harmanci, Arif O., additional, Yang, Jianhua, additional, Klisch, Tiemo J., additional, Li, Xiao-Nan, additional, and Patel, Akash J., additional

Published
2020
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39. Abstract C121: Racial/ethnic differences of pediatric brain tumors in the development of orthotopic PDX models

Author

Qi, Lin, primary, Kogiso, Mari, additional, Du, Yuchen, additional, Huang, Yulun, additional, Zhang, Huiyuan, additional, Braun, Frank, additional, Lindsay, Holly, additional, Zhao, Sibo, additional, Injac, Sarah, additional, Perlaky, Lazlo, additional, Baxter, Patricia, additional, Teo, Wan-Yee, additional, Liu, Zhigang, additional, Zhao, Xiumei, additional, Zhang, Yujing, additional, Su, Jack M.F., additional, and Li, Xiao-Nan, additional

Published
2020
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42. PDTM-17. MiR-126, miR-369-5p AND miR-487b DRIVE PEDIATRIC GLIOBLASTOMA INVASION VIA KCNA1

Author

Huang, Yulun, primary, Qi, Lin, additional, Kogiso, Mari, additional, Du, Yuchen, additional, Braun, Frank, additional, Zhang, Huiyuan, additional, Huang, Lei, additional, Teo, Wan-yee, additional, Lindsay, Holly, additional, zhao, Sibo, additional, Baxter, Patricia, additional, Su, Jack, additional, Adekunle, Adesina, additional, yang, Jianhua, additional, Brabetz, Sebastian, additional, Kool, Marcel, additional, Pfister, Stefan, additional, Chintagumpala, Murali, additional, Parsons, Williams, additional, Perlaky, Laszlo, additional, Wang, Zhong, additional, Zhou, You-Xin, additional, Man, Chris, additional, and Li, Xiao-Nan, additional

Published
2019
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43. DDIS-19. USING MATCHED PRIMARY AND RECURRENT PEDIATRIC BRAIN TUMOR ORTHOTOPIC MOUSE MODELS(PDOX) TO ILLUSTRATE THE GENETIC REVOLUTION AND TO INFORM NEW ANTI-RECURRENT PERSONALIZED THERAPIES

Author

Du, Yuchen, primary, Kogiso, Mari, additional, Braun, Frank, additional, Qi, Lin, additional, zhang, Huiyuan, additional, Lindsay, Holly B, additional, zhao, Sibo, additional, Kool, Marcel, additional, Stephan, Clifford, additional, and Li, Xiaonan, additional

Published
2019
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44. TMOD-21. TARGETING ANAPLASTIC MENINGIOMA WITH PANOBINOSTAT IN PATIENT-DERIVED ORTHOTOPIC XENOGRAFT (PDOX) MODELS DERIVED FROM A MATCHING PAIR OF PRIMARY AND RECURRENT TUMORS

Author

Zhang, Huiyuan, primary, Qi, Lin, additional, Du, Yuchen, additional, Braun, Frank, additional, Kogiso, Mari, additional, Huang, Lei, additional, Klisch, Tiemo, additional, Zhao, Yanling, additional, Guo, Lei, additional, Li, Can, additional, Zhao, Sibo, additional, Lindsay, Holly B, additional, Injac, Sarah, additional, Baxter, Patricia, additional, Su, Jack, additional, Stephan, Clifford, additional, Keller, Charles, additional, Yang, Jianhua, additional, Li, Xiao-Nan, additional, and Patel, Akash, additional

Published
2019
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45. EXTH-45. THERAPEUTIC EFFICACY OF MUTANT ISOCITRATE DEHYDROGENASE 1 (IDH1) INHIBITOR SYC-435 WITH STANDARD THERAPY IN PATIENT-DERIVED IDH1 MUTANT GLIOMA XENOGRAFT MOUSE MODELS

Author

Kogiso, Mari, primary, Qi, Lin, additional, Zhang, Huiyuan, additional, Braun, Frank, additional, Du, Yuchen, additional, Huang, Lei, additional, Guo, Lei, additional, Huang, Yulun, additional, Lindsay, Holly B, additional, Zhao, Sibo, additional, Injac, Sarah, additional, Baxter, Patricia, additional, Su, Jack, additional, Perlaky, Laszlo, additional, Parsons, Williams, additional, Chintagumpala, Murali, additional, Adekunle, Adesina, additional, Wang, Jialiang, additional, Song, Yongcheng, additional, and Li, Xiao-Nan, additional

Published
2019
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46. Abstract LB-320: PPTC testing of an OLIG2 inhibitor CT-179 in patient-derived orthotopic xenograft mouse models of pediatric GBM

Author

Lindsay, Holly, primary, Du, Yuchen, additional, Qi, Lin, additional, Zhang, Huiyuan, additional, Zhao, Sibo, additional, Braun, Frank, additional, Kogiso, Mari, additional, Injac, Sarah, additional, Sobieski, Mary, additional, Stephan, Clifford, additional, Alton, Gordon, additional, Stein, Gregory, additional, Beaton, Graham, additional, Erickson, Stephen, additional, Teicher, Beverly, additional, Smith, Malcolm A., additional, and Li, Xiao-Nan, additional

Published
2019
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48. Transcriptional repressor REST drives lineage stage–specific chromatin compaction at Ptch1 and increases AKT activation in a mouse model of medulloblastoma

Author

Dobson, Tara H. W., primary, Tao, Rong-Hua, additional, Swaminathan, Jyothishmathi, additional, Maegawa, Shinji, additional, Shaik, Shavali, additional, Bravo-Alegria, Javiera, additional, Sharma, Ajay, additional, Kennis, Bridget, additional, Yang, Yanwen, additional, Callegari, Keri, additional, Haltom, Amanda R., additional, Taylor, Pete, additional, Kogiso, Mari, additional, Qi, Lin, additional, Khatua, Soumen, additional, Goldman, Stewart, additional, Lulla, Rishi R., additional, Fangusaro, Jason, additional, MacDonald, Tobey J., additional, Li, Xiao-Nan, additional, Hawkins, Cynthia, additional, Rajaram, Veena, additional, and Gopalakrishnan, Vidya, additional

Published
2019
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49. PDTM-23. CD57 DEFINES A NOVEL MARKER OF GLIOBLASTOMA STEM CELLS THAT DRIVES THE INVASION OF GBM

Author

Qi, Lin, primary, Du, Yuchen, additional, Kogiso, Mari, additional, Braun, Frank, additional, Lindsay, Holly, additional, Zhang, Huiyuan, additional, Zhao, Sibo, additional, Injac, Sarah, additional, Baxter, Patricia, additional, Su, Jack, additional, Mancini, Michael, additional, Hampton, Oliver, additional, Chintagumpala, Murali, additional, Stephan, Clifford, additional, Davies, Peter, additional, and Li, Xiao-Nan, additional

Published
2018
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50. Systems biology–based drug repositioning identifies digoxin as a potential therapy for groups 3 and 4 medulloblastoma

Author

Huang, Lei, primary, Garrett Injac, Sarah, additional, Cui, Kemi, additional, Braun, Frank, additional, Lin, Qi, additional, Du, Yuchen, additional, Zhang, Huiyuan, additional, Kogiso, Mari, additional, Lindsay, Holly, additional, Zhao, Sibo, additional, Baxter, Patricia, additional, Adekunle, Adesina, additional, Man, Tsz-Kwong, additional, Zhao, Hong, additional, Li, Xiao-Nan, additional, Lau, Ching C., additional, and Wong, Stephen T. C., additional

Published
2018
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