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1. Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome.

Author

Thirimanne, H, Almiron-Bonnin, Damian, Nuechterlein, Nicholas, Arora, Sonali, Jensen, Matt, Parada, Carolina, Qiu, Chengxiang, Szulzewsky, Frank, English, Collin, Chen, William, Sievers, Philipp, Nassiri, Farshad, Wang, Justin, Klisch, Tiemo, Aldape, Kenneth, Patel, Akash, Cimino, Patrick, Zadeh, Gelareh, Sahm, Felix, Raleigh, David, Shendure, Jay, Ferreira, Manuel, and Holland, Eric

Subjects
Oncoscape, UMAP, brain tumor, bulk RNA-seq, meningioma, meningioma subtypes, patient prognosis prediction, recurrent, Meningioma, Humans, Transcriptome, Meningeal Neoplasms, Male, Female, Middle Aged, Gene Expression Regulation, Neoplastic, Algorithms, Gene Expression Profiling
Abstract

Meningiomas, although mostly benign, can be recurrent and fatal. World Health Organization (WHO) grading of the tumor does not always identify high-risk meningioma, and better characterizations of their aggressive biology are needed. To approach this problem, we combined 13 bulk RNA sequencing (RNA-seq) datasets to create a dimension-reduced reference landscape of 1,298 meningiomas. The clinical and genomic metadata effectively correlated with landscape regions, which led to the identification of meningioma subtypes with specific biological signatures. The time to recurrence also correlated with the map location. Further, we developed an algorithm that maps new patients onto this landscape, where the nearest neighbors predict outcome. This study highlights the utility of combining bulk transcriptomic datasets to visualize the complexity of tumor populations. Further, we provide an interactive tool for understanding the disease and predicting patient outcomes. This resource is accessible via the online tool Oncoscape, where the scientific community can explore the meningioma landscape.

Published
2024

2. A deep-learning framework to predict cancer treatment response from histopathology images through imputed transcriptomics

Author

Hoang, Danh-Tai, Dinstag, Gal, Shulman, Eldad D., Hermida, Leandro C., Ben-Zvi, Doreen S., Elis, Efrat, Caley, Katherine, Sammut, Stephen-John, Sinha, Sanju, Sinha, Neelam, Dampier, Christopher H., Stossel, Chani, Patil, Tejas, Rajan, Arun, Lassoued, Wiem, Strauss, Julius, Bailey, Shania, Allen, Clint, Redman, Jason, Beker, Tuvik, Jiang, Peng, Golan, Talia, Wilkinson, Scott, Sowalsky, Adam G., Pine, Sharon R., Caldas, Carlos, Gulley, James L., Aldape, Kenneth, Aharonov, Ranit, Stone, Eric A., and Ruppin, Eytan

Published
2024
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3. Virtual multi-institutional tumor board: a strategy for personalized diagnoses and management of rare CNS tumors.

Author

Rogers, James, Wall, Thomas, Acquaye-Mallory, Alvina, Boris, Lisa, Kim, Yeonju, Aldape, Kenneth, Quezado, Martha, Butman, John, Smirniotopoulos, James, Chaudhry, Huma, Tsien, Christina, Chittiboina, Prashant, Zaghloul, Kareem, Aboud, Orwa, Avgeropoulos, Nicholas, Burton, Eric, Cachia, David, Dixit, Karan, Drappatz, Jan, Dunbar, Erin, Forsyth, Peter, Komlodi-Pasztor, Edina, Mandel, Jacob, Ozer, Byram, Lee, Eudocia, Ranjan, Surabhi, Lukas, Rimas, Raygada, Margarita, Salacz, Michael, Smith-Cohn, Matthew, Snyder, James, Soldatos, Ariane, Theeler, Brett, Widemann, Brigitte, Camphausen, Kevin, Heiss, John, Armstrong, Terri, Gilbert, Mark, and Penas-Prado, Marta

Subjects
Barriers to healthcare access, Collaborative practice, Multidisciplinary tumor boards, National Cancer Institute-Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT), Rare CNS tumors, Humans, Retrospective Studies, Pandemics, Central Nervous System Neoplasms, Patient Care Team, Referral and Consultation
Abstract

PURPOSE: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers. METHODS: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions. RESULTS: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions. CONCLUSION: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management.

Published
2024

4. Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion.

Author

Andreiuolo, Felipe, Ferrone, Christina, Rajan, Sharika, Guney, Ekin, Cham, Elaine, Giannini, Caterina, Toland, Angus, Willard, Nicholas, de Souza, Andrea, Dazelle, Karen, Chung, Hye-Jung, Singh, Omkar, Conway, Kyle, Coley, Nicholas, Dampier, Christopher, Abdullaev, Zied, Pratt, Drew, Cimino, Patrick, Quezado, Martha, Aldape, Kenneth, and Perry, Arie

Subjects
BRD4::LEUTX, Embryonal tumor, Methylation, Humans, Brain Neoplasms, Nuclear Proteins, Transcription Factors, Central Nervous System Neoplasms, Neoplasms, Germ Cell and Embryonal, Bromodomain Containing Proteins, Cell Cycle Proteins, Forkhead Transcription Factors, Homeodomain Proteins
Abstract

Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use of methylation profiling and next-generation sequencing has led to the identification of molecularly distinct subtypes. One proposed tumor type, CNS tumor with BRD4::LEUTX fusion, has been described. As only a few CNS tumors with BRD4::LEUTX fusions have been described, we herein characterize a cohort of 9 such cases (4 new, 5 previously published) to further describe their clinicopathologic and molecular features. We demonstrate that CNS embryonal tumor with BRD4::LEUTX fusion comprises a well-defined methylation class/cluster. We find that patients are young (4 years or younger), with large tumors at variable locations, and frequently with evidence of leptomeningeal/cerebrospinal fluid (CSF) dissemination. Histologically, tumors were highly cellular with high-grade embryonal features. Immunohistochemically, 5/5 cases showed synaptophysin and 4/5 showed OLIG2 expression, thus overlapping with CNS neuroblastoma, FOXR2-activated. DNA copy number profiles were generally flat; however, two tumors had chromosome 1q gains. No recurring genomic changes, besides the presence of the fusion, were found. The LEUTX portion of the fusion transcript was constant in all cases assessed, while the BRD4 portion varied but included a domain with proto-oncogenic activity in all cases. Two patients with clinical follow up available had tumors with excellent response to chemotherapy. Two of our patients were alive without evidence of recurrence or progression after gross total resection and chemotherapy at 16 and 33 months. One patient relapsed, and the last of our four patients died of disease one month after diagnosis. Overall, this case series provides additional evidence for this as a distinct tumor type defined by the presence of a specific fusion as well as a distinct DNA methylation signature. Studies on larger series are required to further characterize these tumors.

Published
2024

5. PERCEPTION predicts patient response and resistance to treatment using single-cell transcriptomics of their tumors

Author

Sinha, Sanju, Vegesna, Rahulsimham, Mukherjee, Sumit, Kammula, Ashwin V., Dhruba, Saugato Rahman, Wu, Wei, Kerr, D. Lucas, Nair, Nishanth Ulhas, Jones, Matthew G., Yosef, Nir, Stroganov, Oleg V., Grishagin, Ivan, Aldape, Kenneth D., Blakely, Collin M., Jiang, Peng, Thomas, Craig J., Benes, Cyril H., Bivona, Trever G., Schäffer, Alejandro A., and Ruppin, Eytan

Published
2024
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9. Utility of Immunohistochemistry With Antibodies to SS18-SSX Chimeric Proteins and C-Terminus of SSX Protein for Synovial Sarcoma Differential Diagnosis

Author

Lasota, Jerzy, Chłopek, Małgorzata, Kaczorowski, Maciej, Natálie, Klubíčková, Ryś, Janusz, Kopczyński, Janusz, Sulaieva, Oksana, Michal, Michael, Kruczak, Anna, Harazin-Lechowska, Agnieszka, Szczepaniak, Magdalena, Koshyk, Olena, Hałoń, Agnieszka, Czapiewski, Piotr, Abdullaev, Zied, Kowalik, Artur, Aldape, Kenneth D., Michal, Michal, and Miettinen, Markku

Published
2024
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11. Transcriptome-based response predictor to identify potential responders among patients with negative standard markers for response to immune checkpoint blockers.

Author

Dinstag, Gal, primary, Elis, Efrat, additional, Ben-Zvi, Doreen S., additional, Elia, Anna, additional, Rajagopal, Padma Sheila, additional, Aldape, Kenneth D., additional, Ruppin, Eytan, additional, Pikarsky, Eli, additional, Popovtzer, Aron, additional, Arnon, Johnathan, additional, Beker, Tuvik, additional, and Aharonov, Ranit, additional

Published
2024
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12. Radiotherapy Plan Quality Assurance in NRG Oncology Trials for Brain and Head/Neck Cancers: An AI-Enhanced Knowledge-Based Approach

Author

Wang, Du, primary, Geng, Huaizhi, additional, Gondi, Vinai, additional, Lee, Nancy Y., additional, Tsien, Christina I., additional, Xia, Ping, additional, Chenevert, Thomas L., additional, Michalski, Jeff M., additional, Gilbert, Mark R., additional, Le, Quynh-Thu, additional, Omuro, Antonio M., additional, Men, Kuo, additional, Aldape, Kenneth D., additional, Cao, Yue, additional, Srinivasan, Ashok, additional, Barani, Igor J., additional, Sachdev, Sean, additional, Huang, Jiayi, additional, Choi, Serah, additional, Shi, Wenyin, additional, Battiste, James D., additional, Wardak, Zabi, additional, Chan, Michael D., additional, Mehta, Minesh P., additional, and Xiao, Ying, additional

Published
2024
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13. Supplementary Table S3 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma

Author

Schreck, Karisa C., primary, Strowd, Roy E., primary, Nabors, Louis B., primary, Ellingson, Benjamin M., primary, Chang, Michael, primary, Tan, Sze K., primary, Abdullaev, Zied, primary, Turakulov, Rust, primary, Aldape, Kenneth, primary, Danda, Neeraja, primary, Desideri, Serena, primary, Fisher, Joy, primary, Iacoboni, Michaella, primary, Surakus, Trisha, primary, Rudek, Michelle A., primary, Bettegowda, Chetan, primary, Grossman, Stuart A., primary, and Ye, Xiaobu, primary

Published
2024
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14. Supplementary Figure S3 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma

Author

Schreck, Karisa C., primary, Strowd, Roy E., primary, Nabors, Louis B., primary, Ellingson, Benjamin M., primary, Chang, Michael, primary, Tan, Sze K., primary, Abdullaev, Zied, primary, Turakulov, Rust, primary, Aldape, Kenneth, primary, Danda, Neeraja, primary, Desideri, Serena, primary, Fisher, Joy, primary, Iacoboni, Michaella, primary, Surakus, Trisha, primary, Rudek, Michelle A., primary, Bettegowda, Chetan, primary, Grossman, Stuart A., primary, and Ye, Xiaobu, primary

Published
2024
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15. Supplementary Material 1 from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma

Author

Schreck, Karisa C., primary, Strowd, Roy E., primary, Nabors, Louis B., primary, Ellingson, Benjamin M., primary, Chang, Michael, primary, Tan, Sze K., primary, Abdullaev, Zied, primary, Turakulov, Rust, primary, Aldape, Kenneth, primary, Danda, Neeraja, primary, Desideri, Serena, primary, Fisher, Joy, primary, Iacoboni, Michaella, primary, Surakus, Trisha, primary, Rudek, Michelle A., primary, Bettegowda, Chetan, primary, Grossman, Stuart A., primary, and Ye, Xiaobu, primary

Published
2024
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16. Data from Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma

Author

Schreck, Karisa C., primary, Strowd, Roy E., primary, Nabors, Louis B., primary, Ellingson, Benjamin M., primary, Chang, Michael, primary, Tan, Sze K., primary, Abdullaev, Zied, primary, Turakulov, Rust, primary, Aldape, Kenneth, primary, Danda, Neeraja, primary, Desideri, Serena, primary, Fisher, Joy, primary, Iacoboni, Michaella, primary, Surakus, Trisha, primary, Rudek, Michelle A., primary, Bettegowda, Chetan, primary, Grossman, Stuart A., primary, and Ye, Xiaobu, primary

Published
2024
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17. The biological significance of tumor grade, age, enhancement, and extent of resection in IDH-mutant gliomas: How should they inform treatment decisions in the era of IDH inhibitors?

Author

Bent, Martin J van den, French, Pim J, Brat, Daniel, Tonn, Joerg C, Touat, Mehdi, Ellingson, Benjamin M, Young, Robert J, Pallud, Johan, Deimling, Andreas von, Sahm, Felix, Branger, Dominique Figarella, Huang, Raymond Y, Weller, Michael, Mellinghoff, Ingo K, Cloughsey, Tim F, Huse, Jason T, Aldape, Kenneth, Reifenberger, Guido, Youssef, Gilbert, and Karschnia, Philipp

Published
2024
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18. HOXD12 defines an age-related aggressive subtype of oligodendroglioma.

Author

Nuechterlein, Nicholas, Cimino, Sadie, Shelbourn, Allison, Ha, Vinny, Arora, Sonali, Rajan, Sharika, Shapiro, Linda G., Holland, Eric C., Aldape, Kenneth, McGranahan, Tresa, Gilbert, Mark R., and Cimino, Patrick J.

Subjects
GENE expression, DNA analysis, DNA methylation, AGE distribution, OLDER patients
Abstract

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted has highly variable outcomes that are strongly influenced by patient age. The distribution of oligodendroglioma age is non-Gaussian and reportedly bimodal, which motivated our investigation of age-associated molecular alterations that may drive poorer outcomes. We found that elevated HOXD12 expression was associated with both older patient age and shorter survival in the TCGA (FDR < 0.01, FDR = 1e−5) and the CGGA (p = 0.03, p < 1e−3). HOXD12 gene body hypermethylation was associated with older age, higher WHO grade, and shorter survival in the TCGA (p < 1e−6, p < 0.001, p < 1e−3) and with older age and higher WHO grade in Capper et al. (p < 0.002, p = 0.014). In the TCGA, HOXD12 gene body hypermethylation and elevated expression were independently prognostic of NOTCH1 and PIK3CA mutations, loss of 15q, MYC activation, and standard histopathological features. Single-nucleus RNA and ATAC sequencing data showed that HOXD12 activity was elevated in neoplastic tissue, particularly within cycling and OPC-like cells, and was associated with a stem-like phenotype. A pan-HOX DNA methylation analysis revealed an age and survival-associated HOX-high signature that was tightly associated with HOXD12 gene body methylation. Overall, HOXD12 expression and gene body hypermethylation were associated with an older, atypically aggressive subtype of oligodendroglioma. [ABSTRACT FROM AUTHOR]

Published
2024
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20. Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma

Author

Schreck, Karisa C., primary, Strowd, Roy E., additional, Nabors, Louis B., additional, Ellingson, Benjamin M., additional, Chang, Michael, additional, Tan, Sze K., additional, Abdullaev, Zied, additional, Turakulov, Rust, additional, Aldape, Kenneth, additional, Danda, Neeraja, additional, Desideri, Serena, additional, Fisher, Joy, additional, Iacoboni, Michaella, additional, Surakus, Trisha, additional, Rudek, Michelle A., additional, Bettegowda, Chetan, additional, Grossman, Stuart A., additional, and Ye, Xiaobu, additional

Published
2024
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21. 379 Meningioma Molecular Groups Predict Response to Adjuvant Radiotherapy Following Surgery

Author

Wang, Justin Z., primary, Nassiri, Farshad, additional, Patil, Vikas, additional, Landry, Alexander, additional, Liu, Jeffrey, additional, Cohen-Gadol, Aaron A., additional, Barnholtz-Sloan, Jill, additional, Tabatabai, Ghazaleh, additional, Chotai, Silky, additional, Sahm, Felix, additional, Aldape, Kenneth, additional, and Zadeh, Gelareh, additional

Published
2024
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22. Table S1 from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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23. Supp Figures from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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24. Supplemental Figures Legends from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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25. Data from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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26. Supplementary Appendix from The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., primary, Sabedot, Thais S., primary, Morosini, Natalia S., primary, Datta, Indrani, primary, Garofano, Luciano, primary, Vallentgoed, Wies, primary, Varn, Frederick S., primary, Aldape, Kenneth, primary, D'Angelo, Fulvio, primary, Bakas, Spyridon, primary, Barnholtz-Sloan, Jill S., primary, Gan, Hui K., primary, Hasanain, Mohammad, primary, Hau, Ann-Christin, primary, Johnson, Kevin C., primary, Cazacu, Simona, primary, deCarvalho, Ana C., primary, Khasraw, Mustafa, primary, Kocakavuk, Emre, primary, Kouwenhoven, Mathilde C.M., primary, Migliozzi, Simona, primary, Niclou, Simone P., primary, Niers, Johanna M., primary, Ormond, D. Ryan, primary, Paek, Sun Ha, primary, Reifenberger, Guido, primary, Sillevis Smitt, Peter A., primary, Smits, Marion, primary, Stead, Lucy F., primary, van den Bent, Martin J., primary, Van Meir, Erwin G., primary, Walenkamp, Annemiek, primary, Weiss, Tobias, primary, Weller, Michael, primary, Westerman, Bart A., primary, Ylstra, Bauke, primary, Wesseling, Pieter, primary, Lasorella, Anna, primary, French, Pim J., primary, Poisson, Laila M., primary, Woehrer, Adelheid, primary, Lowman, Allison K, primary, deCarvalho, Ana C, primary, Castro, Ana Valeria, primary, Transou, Andrea, primary, Brodbelt, Andrew R, primary, Golebiewska, Anna, primary, Molinaro, Annette M, primary, Iavarone, Antonio, primary, Ismail, Azzam, primary, Westerman, Bart A, primary, Bock, Christoph, primary, Brat, Daniel J, primary, Van Meir, Erwin G, primary, Barthel, Floris P, primary, Varn, Frederick S, primary, Finocchiaro, Gaetano, primary, Rao, Ganesh, primary, Zadeh, Gelareh, primary, ngNg, Ho Keu, primary, Kim, Hoon, primary, Noushmehr, Houtan, primary, Miletic, Hrvoje, primary, Gan, Hui K, primary, Rock, Jack, primary, Snyder, James M, primary, Huse, Jason T, primary, Connelly, Jennifer M, primary, Barnholtz-Sloan, Jill S, primary, Niers, Johanna M, primary, deGroot, John F, primary, Akdemir, Kadir C, primary, Kannan, Kasthuri S, primary, Ligon, Keith L, primary, Bulsara, Ketan R, primary, Johnson, Kevin C, primary, Alfaro, Kristin D, primary, Poisson, Laila M, primary, Stead, Lucy F, primary, Nasrallah, MacLean P, primary, van den Bent, Martin J, primary, Kouwenhoven, Mathilde CM, primary, Gould, Peter V, primary, Smitt, Peter A Sillevis, primary, LaViolette, Peter S, primary, Tatman, Philip D, primary, French, Pim J, primary, Beroukhim, Rameen, primary, Verhaak, Roel G.W., primary, Niclou, Simone P, primary, Kalkanis, Steven, primary, Short, Susan C, primary, Ghazaleh, Tabatabai, primary, Malta, Tathiane M, primary, Sabedot, Thais S, primary, Walbert, Tobias, primary, Baid, Ujjwal, primary, and Yung, W. K. Alfred, primary

Published
2024
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27. Meningioma transcriptomic landscape demonstrates novel subtypes with regional associated biology and patient outcome.

Author

Thirimanne, H. Nayanga, primary, Bonnin, Damian Almiron, additional, Nuechterlein, Nicholas, additional, Arora, Sonali, additional, Jensen, Matt, additional, Parada, Carolina A, additional, Qiu, Chengxiang, additional, Szulzewsky, Frank, additional, English, Collin W, additional, Chen, William C, additional, Sievers, Philipp, additional, Nassiri, Farshad, additional, Wang, Justin Z, additional, Klisch, Tiemo J, additional, Aldape, Kenneth D, additional, Patel, Akash J, additional, Cimino, Patrick J, additional, Zadeh, Gelareh, additional, Sahm, Felix, additional, Raleigh, David R, additional, Shendure, Jay, additional, Ferreira, Manuel, additional, and Holland, Eric C, additional

Published
2024
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28. The outcomes measured and reported in intracranial meningioma clinical trials: A systematic review

Author

Millward, Christopher P; https://orcid.org/0000-0001-7727-1157, Keshwara, Sumirat M, Armstrong, Terri S; https://orcid.org/0000-0002-2414-0492, Barrington, Heather; https://orcid.org/0000-0001-9103-2670, Bell, Sabrina, Brodbelt, Andrew R, Bulbeck, Helen, Dirven, Linda; https://orcid.org/0000-0001-9157-9895, Grundy, Paul L, Islim, Abdurrahman I, Javadpour, Mohsen, Koszdin, Shelli D, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Plaha, Puneet, Preusser, Matthias; https://orcid.org/0000-0003-3541-2315, Santarius, Thomas, Srikandarajah, Nisaharan; https://orcid.org/0000-0001-9578-508X, Taphoorn, Martin J B; https://orcid.org/0000-0001-9949-4722, Turner, Carole, Watts, Colin; https://orcid.org/0000-0003-3531-8791, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Williamson, Paula R, Zadeh, Gelareh; https://orcid.org/0000-0002-6637-4502, Zamanipoor Najafabadi, Amir H, Jenkinson, Michael D, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, et al, Millward, Christopher P; https://orcid.org/0000-0001-7727-1157, Keshwara, Sumirat M, Armstrong, Terri S; https://orcid.org/0000-0002-2414-0492, Barrington, Heather; https://orcid.org/0000-0001-9103-2670, Bell, Sabrina, Brodbelt, Andrew R, Bulbeck, Helen, Dirven, Linda; https://orcid.org/0000-0001-9157-9895, Grundy, Paul L, Islim, Abdurrahman I, Javadpour, Mohsen, Koszdin, Shelli D, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Plaha, Puneet, Preusser, Matthias; https://orcid.org/0000-0003-3541-2315, Santarius, Thomas, Srikandarajah, Nisaharan; https://orcid.org/0000-0001-9578-508X, Taphoorn, Martin J B; https://orcid.org/0000-0001-9949-4722, Turner, Carole, Watts, Colin; https://orcid.org/0000-0003-3531-8791, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Williamson, Paula R, Zadeh, Gelareh; https://orcid.org/0000-0002-6637-4502, Zamanipoor Najafabadi, Amir H, Jenkinson, Michael D, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, and et al

Abstract

Background Meningioma clinical trials have assessed interventions including surgery, radiotherapy, and pharmacotherapy. However, agreement does not exist on what, how, and when outcomes of interest should be measured. To do so would allow comparative analysis of similar trials. This systematic review aimed to summarize the outcomes measured and reported in meningioma clinical trials. Methods Systematic literature and trial registry searches were performed to identify published and ongoing intracranial meningioma clinical trials (PubMed, Embase, Medline, CINAHL via EBSCO, and Web of Science, completed January 22, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were deduplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the “Core Outcome Measures in Effectiveness Trials” (COMET) initiative. Results Thirty published articles and 18 ongoing studies were included, describing 47 unique clinical trials: Phase 2 n = 33, phase 3 n = 14. Common interventions included: Surgery n = 13, radiotherapy n = 8, and pharmacotherapy n = 20. In total, 659 verbatim outcomes were reported, of which 84 were defined. Following de-duplication, 415 unique verbatim outcomes remained and were grouped into 115 standardized outcome terms. These were classified using the COMET taxonomy into 29 outcome domains and 5 core areas. Conclusions Outcome measurement across meningioma clinical trials is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a core outcome set for use in future meningioma clinical trials.

Published
2024

29. The outcomes measured and reported in observational studies of incidental and untreated intracranial meningioma: A systematic review

Author

Millward, Christopher P; https://orcid.org/0000-0001-7727-1157, Islim, Abdurrahman I, Armstrong, Terri S; https://orcid.org/0000-0002-2414-0492, Barrington, Heather; https://orcid.org/0000-0001-9103-2670, Bell, Sabrina, Brodbelt, Andrew R, Bulbeck, Helen, Dirven, Linda; https://orcid.org/0000-0001-9157-9895, Grundy, Paul L, Javadpour, Mohsen, Keshwara, Sumirat M, Koszdin, Shelli D, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Plaha, Puneet, Preusser, Matthias; https://orcid.org/0000-0003-3541-2315, Santarius, Thomas, Srikandarajah, Nisaharan; https://orcid.org/0000-0001-9578-508X, Taphoorn, Martin J B; https://orcid.org/0000-0001-9949-4722, Turner, Carole, Watts, Colin; https://orcid.org/0000-0003-3531-8791, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Williamson, Paula R, Zadeh, Gelareh; https://orcid.org/0000-0002-6637-4502, Zamanipoor Najafabadi, Amir H, Jenkinson, Michael D, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, et al, Millward, Christopher P; https://orcid.org/0000-0001-7727-1157, Islim, Abdurrahman I, Armstrong, Terri S; https://orcid.org/0000-0002-2414-0492, Barrington, Heather; https://orcid.org/0000-0001-9103-2670, Bell, Sabrina, Brodbelt, Andrew R, Bulbeck, Helen, Dirven, Linda; https://orcid.org/0000-0001-9157-9895, Grundy, Paul L, Javadpour, Mohsen, Keshwara, Sumirat M, Koszdin, Shelli D, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Plaha, Puneet, Preusser, Matthias; https://orcid.org/0000-0003-3541-2315, Santarius, Thomas, Srikandarajah, Nisaharan; https://orcid.org/0000-0001-9578-508X, Taphoorn, Martin J B; https://orcid.org/0000-0001-9949-4722, Turner, Carole, Watts, Colin; https://orcid.org/0000-0003-3531-8791, Weller, Michael; https://orcid.org/0000-0002-1748-174X, Williamson, Paula R, Zadeh, Gelareh; https://orcid.org/0000-0002-6637-4502, Zamanipoor Najafabadi, Amir H, Jenkinson, Michael D, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, and et al

Abstract

Background The clinical management of patients with incidental intracranial meningioma varies markedly and is often based on clinician choice and observational data. Heterogeneous outcome measurement has likely hampered knowledge progress by preventing comparative analysis of similar cohorts of patients. This systematic review aimed to summarize the outcomes measured and reported in observational studies. Methods A systematic literature search was performed to identify published full texts describing active monitoring of adult cohorts with incidental and untreated intracranial meningioma (PubMed, EMBASE, MEDLINE, and CINAHL via EBSCO, completed January 24, 2022). Reported outcomes were extracted verbatim, along with an associated definition and method of measurement if provided. Verbatim outcomes were de-duplicated and the resulting unique outcomes were grouped under standardized outcome terms. These were classified using the taxonomy proposed by the “Core Outcome Measures in Effectiveness Trials” (COMET) initiative. Results Thirty-three published articles and 1 ongoing study were included describing 32 unique studies: study designs were retrospective n = 27 and prospective n = 5. In total, 268 verbatim outcomes were reported, of which 77 were defined. Following de-duplication, 178 unique verbatim outcomes remained and were grouped into 53 standardized outcome terms. These were classified using the COMET taxonomy into 9 outcome domains and 3 core areas. Conclusions Outcome measurement across observational studies of incidental and untreated intracranial meningioma is heterogeneous. The standardized outcome terms identified will be prioritized through an eDelphi survey and consensus meeting of key stakeholders (including patients), in order to develop a Core Outcome Set for use in future observational studies.

Published
2024

30. The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen

Author

Malta, Tathiane M; https://orcid.org/0000-0003-1129-5791, Sabedot, Thais S; https://orcid.org/0000-0002-7813-483X, Morosini, Natalia S; https://orcid.org/0000-0002-9294-9461, Datta, Indrani; https://orcid.org/0000-0001-7548-9881, Garofano, Luciano; https://orcid.org/0000-0001-8582-0865, Vallentgoed, Wies R; https://orcid.org/0000-0001-6373-7710, Varn, Frederick S; https://orcid.org/0000-0001-6307-016X, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, D'Angelo, Fulvio; https://orcid.org/0000-0002-4940-4693, Bakas, Spyridon; https://orcid.org/0000-0001-8734-6482, Barnholtz-Sloan, Jill S; https://orcid.org/0000-0001-6190-9304, Gan, Hui K; https://orcid.org/0000-0001-7319-8546, Hasanain, Mohammad; https://orcid.org/0000-0001-5207-101X, Hau, Ann-Christin; https://orcid.org/0000-0002-4412-2355, Johnson, Kevin C; https://orcid.org/0000-0003-0016-5158, Cazacu, Simona; https://orcid.org/0000-0002-6085-4177, deCarvalho, Ana C; https://orcid.org/0000-0003-1183-4548, Khasraw, Mustafa; https://orcid.org/0000-0003-3249-9849, Kocakavuk, Emre; https://orcid.org/0000-0003-1920-0494, Kouwenhoven, Mathilde C M; https://orcid.org/0000-0001-5252-4365, Migliozzi, Simona; https://orcid.org/0000-0002-4870-8943, Niclou, Simone P; https://orcid.org/0000-0002-3417-9534, Niers, Johanna M; https://orcid.org/0000-0002-0366-8247, Ormond, D Ryan; https://orcid.org/0000-0001-7027-2915, Paek, Sun Ha; https://orcid.org/0000-0003-3007-8653, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Sillevis Smitt, Peter A; https://orcid.org/0000-0001-8044-6798, Smits, Marion; https://orcid.org/0000-0001-5563-2871, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Weller, Michael; https://orcid.org/0000-0002-1748-174X, et al, Malta, Tathiane M; https://orcid.org/0000-0003-1129-5791, Sabedot, Thais S; https://orcid.org/0000-0002-7813-483X, Morosini, Natalia S; https://orcid.org/0000-0002-9294-9461, Datta, Indrani; https://orcid.org/0000-0001-7548-9881, Garofano, Luciano; https://orcid.org/0000-0001-8582-0865, Vallentgoed, Wies R; https://orcid.org/0000-0001-6373-7710, Varn, Frederick S; https://orcid.org/0000-0001-6307-016X, Aldape, Kenneth; https://orcid.org/0000-0001-5119-7550, D'Angelo, Fulvio; https://orcid.org/0000-0002-4940-4693, Bakas, Spyridon; https://orcid.org/0000-0001-8734-6482, Barnholtz-Sloan, Jill S; https://orcid.org/0000-0001-6190-9304, Gan, Hui K; https://orcid.org/0000-0001-7319-8546, Hasanain, Mohammad; https://orcid.org/0000-0001-5207-101X, Hau, Ann-Christin; https://orcid.org/0000-0002-4412-2355, Johnson, Kevin C; https://orcid.org/0000-0003-0016-5158, Cazacu, Simona; https://orcid.org/0000-0002-6085-4177, deCarvalho, Ana C; https://orcid.org/0000-0003-1183-4548, Khasraw, Mustafa; https://orcid.org/0000-0003-3249-9849, Kocakavuk, Emre; https://orcid.org/0000-0003-1920-0494, Kouwenhoven, Mathilde C M; https://orcid.org/0000-0001-5252-4365, Migliozzi, Simona; https://orcid.org/0000-0002-4870-8943, Niclou, Simone P; https://orcid.org/0000-0002-3417-9534, Niers, Johanna M; https://orcid.org/0000-0002-0366-8247, Ormond, D Ryan; https://orcid.org/0000-0001-7027-2915, Paek, Sun Ha; https://orcid.org/0000-0003-3007-8653, Reifenberger, Guido; https://orcid.org/0000-0002-1419-9837, Sillevis Smitt, Peter A; https://orcid.org/0000-0001-8044-6798, Smits, Marion; https://orcid.org/0000-0001-5563-2871, Weiss, Tobias; https://orcid.org/0000-0002-5533-9429, Weller, Michael; https://orcid.org/0000-0002-1748-174X, and et al

Abstract

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histological progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neo-angiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution towards an IDHwt-like phenotype.

Published
2024

31. The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Author

Malta, Tathiane M., Sabedot, Thais S., Morosini, Natalia S., Datta, Indrani, Garofano, Luciano, Vallentgoed, Wies, Varn, Frederick S., Aldape, Kenneth, D'Angelo, Fulvio, Bakas, Spyridon, Barnholtz-Sloan, Jill S., Gan, Hui K., Hasanain, Mohammad, Hau, Ann Christin, Johnson, Kevin C., Cazacu, Simona, deCarvalho, Ana C., Khasraw, Mustafa, Kocakavuk, Emre, Kouwenhoven, Mathilde C.M., Migliozzi, Simona, Niclou, Simone P., Niers, Johanna M., Ormond, D. Ryan, Paek, Sun Ha, Reifenberger, Guido, Smitt, Peter A.Sillevis, Smits, Marion, Stead, Lucy F., van den Bent, Martin J., Van Meir, Erwin G., Walenkamp, Annemiek, Weiss, Tobias, Weller, Michael, Westerman, Bart A., Ylstra, Bauke, Wesseling, Pieter, Lasorella, Anna, French, Pim J., Poisson, Laila M., Verhaak, Roel G.W., Iavarone, Antonio, Noushmehr, Houtan, Malta, Tathiane M., Sabedot, Thais S., Morosini, Natalia S., Datta, Indrani, Garofano, Luciano, Vallentgoed, Wies, Varn, Frederick S., Aldape, Kenneth, D'Angelo, Fulvio, Bakas, Spyridon, Barnholtz-Sloan, Jill S., Gan, Hui K., Hasanain, Mohammad, Hau, Ann Christin, Johnson, Kevin C., Cazacu, Simona, deCarvalho, Ana C., Khasraw, Mustafa, Kocakavuk, Emre, Kouwenhoven, Mathilde C.M., Migliozzi, Simona, Niclou, Simone P., Niers, Johanna M., Ormond, D. Ryan, Paek, Sun Ha, Reifenberger, Guido, Smitt, Peter A.Sillevis, Smits, Marion, Stead, Lucy F., van den Bent, Martin J., Van Meir, Erwin G., Walenkamp, Annemiek, Weiss, Tobias, Weller, Michael, Westerman, Bart A., Ylstra, Bauke, Wesseling, Pieter, Lasorella, Anna, French, Pim J., Poisson, Laila M., Verhaak, Roel G.W., Iavarone, Antonio, and Noushmehr, Houtan

Abstract

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histologic progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neoangiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution toward an IDHwt-like phenotype.

Published
2024

33. Diffuse hemispheric glioma with H3 p.K28M (K27M) mutation: Unusual non-midline presentation of diffuse midline glioma, H3 K27M-altered?

Author

Donev, Kliment, Sundararajan, Vanitha, Johnson, Derek, Balan, Jagadheshwar, Chambers, Meagan, Paulson, Vera A, Scherpelz, Kathryn P, Abdullaev, Zied, Quezado, Martha, Cimino, Patrick J, Pratt, Drew, Valerio, Ediel, Castro, João Vıctor Alves de, Carraro, Dirce Maria, Torrezan, Giovana Tardin, Wolff, Beatriz Martins, Kulikowski, Leslie Domenici, Costa, Felipe D'Almeida, Aldape, Kenneth, and Ida, Cristiane M

Published
2024
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34. Potential prognostic determinants for FET::CREB fusion-positive intracranial mesenchymal tumor

Author

Mezzacappa, Frank M., primary, Smith, Frankie K., additional, Zhang, Weiwei, additional, Gard, Andrew, additional, Cabuk, Fatmagul Kusku, additional, Gonzalez-Gomez, Ignancio, additional, Monforte, Hector L., additional, Liang, Jiancong, additional, Singh, Omkar, additional, Quezado, Martha M., additional, Aldape, Kenneth D., additional, Gokden, Murat, additional, Bridge, Julia A., additional, and Chen, Jie, additional

Published
2024
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35. Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas

Author

Nair, Nishanth Ulhas, primary, Schaffer, Alejandro A, additional, Gertz, Michael E, additional, Cheng, Kuoyuan, additional, Zerbib, Johanna, additional, Sahu, Avinash Das, additional, Leor, Gil, additional, Shulman, Eldad D, additional, Aldape, Kenneth D, additional, Ben-David, Uri, additional, and Ruppin, Eytan, additional

Published
2024
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36. Data from Impact of Rare and Multiple Concurrent Gene Fusions on Diagnostic DNA Methylation Classifier in Brain Tumors

Author

Galbraith, Kristyn, primary, Serrano, Jonathan, primary, Shen, Guomiao, primary, Tran, Ivy, primary, Slocum, Cheyanne C., primary, Ketchum, Courtney, primary, Abdullaev, Zied, primary, Turakulov, Rust, primary, Bale, Tejus, primary, Ladanyi, Marc, primary, Sukhadia, Purvil, primary, Zaidinski, Michael, primary, Mullaney, Kerry, primary, DiNapoli, Sara, primary, Liechty, Benjamin L., primary, Barbaro, Marissa, primary, Allen, Jeffrey C., primary, Gardner, Sharon L., primary, Wisoff, Jeffrey, primary, Harter, David, primary, Hidalgo, Eveline Teresa, primary, Golfinos, John G., primary, Orringer, Daniel A., primary, Aldape, Kenneth, primary, Benhamida, Jamal, primary, Wrzeszczynski, Kazimierz O., primary, Jour, George, primary, and Snuderl, Matija, primary

Published
2024
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37. Supplementary Table 2 from Impact of Rare and Multiple Concurrent Gene Fusions on Diagnostic DNA Methylation Classifier in Brain Tumors

Author

Galbraith, Kristyn, primary, Serrano, Jonathan, primary, Shen, Guomiao, primary, Tran, Ivy, primary, Slocum, Cheyanne C., primary, Ketchum, Courtney, primary, Abdullaev, Zied, primary, Turakulov, Rust, primary, Bale, Tejus, primary, Ladanyi, Marc, primary, Sukhadia, Purvil, primary, Zaidinski, Michael, primary, Mullaney, Kerry, primary, DiNapoli, Sara, primary, Liechty, Benjamin L., primary, Barbaro, Marissa, primary, Allen, Jeffrey C., primary, Gardner, Sharon L., primary, Wisoff, Jeffrey, primary, Harter, David, primary, Hidalgo, Eveline Teresa, primary, Golfinos, John G., primary, Orringer, Daniel A., primary, Aldape, Kenneth, primary, Benhamida, Jamal, primary, Wrzeszczynski, Kazimierz O., primary, Jour, George, primary, and Snuderl, Matija, primary

Published
2024
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39. Supplementary Table 1 from Impact of Rare and Multiple Concurrent Gene Fusions on Diagnostic DNA Methylation Classifier in Brain Tumors

Author

Galbraith, Kristyn, primary, Serrano, Jonathan, primary, Shen, Guomiao, primary, Tran, Ivy, primary, Slocum, Cheyanne C., primary, Ketchum, Courtney, primary, Abdullaev, Zied, primary, Turakulov, Rust, primary, Bale, Tejus, primary, Ladanyi, Marc, primary, Sukhadia, Purvil, primary, Zaidinski, Michael, primary, Mullaney, Kerry, primary, DiNapoli, Sara, primary, Liechty, Benjamin L., primary, Barbaro, Marissa, primary, Allen, Jeffrey C., primary, Gardner, Sharon L., primary, Wisoff, Jeffrey, primary, Harter, David, primary, Hidalgo, Eveline Teresa, primary, Golfinos, John G., primary, Orringer, Daniel A., primary, Aldape, Kenneth, primary, Benhamida, Jamal, primary, Wrzeszczynski, Kazimierz O., primary, Jour, George, primary, and Snuderl, Matija, primary

Published
2024
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40. Long-term survivors of glioblastoma: Tumor molecular, clinical, and imaging findings

Author

Briceno, Nicole, primary, Vera, Elizabeth, additional, Komlodi-Pasztor, Edina, additional, Abdullaev, Zied, additional, Choi, Anna, additional, Grajkowska, Ewa, additional, Kunst, Tricia, additional, Levine, Jason, additional, Lindsley, Matthew, additional, Fernandez, Kelly, additional, Reyes, Jennifer, additional, Boris, Lisa, additional, Burton, Eric, additional, Panzer, Marissa, additional, Polskin, Lily, additional, Penas-Prado, Marta, additional, Pillai, Tina, additional, Theeler, Brett J, additional, Wu, Jing, additional, Wall, Kathleen, additional, Papanicolau-Sengos, Antonios, additional, Quezado, Martha, additional, Smirniotopoulos, James, additional, Aldape, Kenneth, additional, Armstrong, Terri S, additional, and Gilbert, Mark R, additional

Published
2024
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43. Prediction of DNA methylation-based tumor types from histopathology in central nervous system tumors with deep learning

Author

Hoang, Danh-Tai, Shulman, Eldad D., Turakulov, Rust, Abdullaev, Zied, Singh, Omkar, Campagnolo, Emma M., Lalchungnunga, H., Stone, Eric A., Nasrallah, MacLean P., Ruppin, Eytan, and Aldape, Kenneth

Abstract

Precision in the diagnosis of diverse central nervous system (CNS) tumor types is crucial for optimal treatment. DNA methylation profiles, which capture the methylation status of thousands of individual CpG sites, are state-of-the-art data-driven means to enhance diagnostic accuracy but are also time consuming and not widely available. Here, to address these limitations, we developed Deep lEarning from histoPathoLOgy and methYlation (DEPLOY), a deep learning model that classifies CNS tumors to ten major categories from histopathology. DEPLOY integrates three distinct components: the first classifies CNS tumors directly from slide images (‘direct model’), the second initially generates predictions for DNA methylation beta values, which are subsequently used for tumor classification (‘indirect model’), and the third classifies tumor types directly from routinely available patient demographics. First, we find that DEPLOY accurately predicts beta values from histopathology images. Second, using a ten-class model trained on an internal dataset of 1,796 patients, we predict the tumor categories in three independent external test datasets including 2,156 patients, achieving an overall accuracy of 95% and balanced accuracy of 91% on samples that are predicted with high confidence. These results showcase the potential future use of DEPLOY to assist pathologists in diagnosing CNS tumors within a clinically relevant short time frame.

Published
2024
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44. Haploinsufficiency of phosphodiesterase 10A activates PI3K/AKT signaling independent of PTEN to induce an aggressive glioma phenotype

Author

Nuechterlein, Nicholas, Shelbourn, Allison, Szulzewsky, Frank, Arora, Sonali, Casad, Michelle, Pattwell, Siobhan, Merino-Galan, Leyre, Sulman, Erik, Arowa, Sumaita, Alvinez, Neriah, Jung, Miyeon, Brown, Desmond, Tang, Kayen, Jackson, Sadhana, Stoica, Stefan, Chittaboina, Prashant, Banasavadi-Siddegowda, Yeshavanth K., Wirsching, Hans-Georg, Stella, Nephi, Shapiro, Linda, Paddison, Patrick, Patel, Anoop P., Gilbert, Mark R., Abdullaev, Zied, Aldape, Kenneth, Pratt, Drew, Holland, Eric C., and Cimino, Patrick J.

Abstract

In this study, Nuechterlein et al. show that the deficiency of phosphodiesterase PDE10A activates PI3K/AKT/mTOR signaling independent of PTEN and promotes proneural-to-mesenchymal transition and gliomagenesis. Their work highlights that PDE10A may function as a potential tumor suppressor and that PDE10A-deficient glioblastomas may be therapeutically vulnerable to PI3K inhibition.

Published
2024
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45. Molecular classification to refine surgical and radiotherapeutic decision-making in meningioma

Author

Wang, Justin Z., Patil, Vikas, Landry, Alexander P., Gui, Chloe, Ajisebutu, Andrew, Liu, Jeff, Saarela, Olli, Pugh, Stephanie L., Won, Minhee, Patel, Zeel, Yakubov, Rebeca, Kaloti, Ramneet, Wilson, Christopher, Cohen-Gadol, Aaron, Zaazoue, Mohamed A., Tabatabai, Ghazaleh, Tatagiba, Marcos, Behling, Felix, Almiron Bonnin, Damian A., Holland, Eric C., Kruser, Tim J., Barnholtz-Sloan, Jill S., Sloan, Andrew E., Horbinski, Craig, Chotai, Silky, Chambless, Lola B., Gao, Andrew, Rebchuk, Alexander D., Makarenko, Serge, Yip, Stephen, Sahm, Felix, Maas, Sybren L. N., Tsang, Derek S., Rogers, C. Leland, Aldape, Kenneth, Nassiri, Farshad, and Zadeh, Gelareh

Abstract

Treatment of the tumor and dural margin with surgery and sometimes radiation are cornerstones of therapy for meningioma. Molecular classifications have provided insights into the biology of disease; however, response to treatment remains heterogeneous. In this study, we used retrospective data on 2,824 meningiomas, including molecular data on 1,686 tumors and 100 prospective meningiomas, from the RTOG-0539 phase 2 trial to define molecular biomarkers of treatment response. Using propensity score matching, we found that gross tumor resection was associated with longer progression-free survival (PFS) across all molecular groups and longer overall survival in proliferative meningiomas. Dural margin treatment (Simpson grade 1/2) prolonged PFS compared to no treatment (Simpson grade 3). Molecular group classification predicted response to radiotherapy, including in the RTOG-0539 cohort. We subsequently developed a molecular model to predict response to radiotherapy that discriminates outcome better than standard-of-care classification. This study highlights the potential for molecular profiling to refine surgical and radiotherapy decision-making.

Published
2024
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48. A case of myxopapillary ependymoma with predominant giant cell morphology: A rare entity with comprehensive genomic profiling and review of literature.

Author

Morales‐Vargas, Bryan, Saad, Hassan, Refai, Daniel, Schniederjan, Matthew, Abdullaev, Zied, Aldape, Kenneth, and Abedalthagafi, Malak

Abstract

In the evolving landscape of ependymoma classification, which integrates histological, molecular, and anatomical context, we detail a rare case divergent from the usual histopathological spectrum. We present the case of a 37‐year‐old man with symptomatic spinal cord compression at the L3–L4 level. Neuroradiological evaluation revealed an intradural, encapsulated mass. Histologically, the tumor displayed atypical features: bizarre pleomorphic giant cells, intranuclear inclusions, mitotic activity, and a profusion of eosinophilic cytoplasm with hyalinized vessels, deviating from the characteristic perivascular pseudorosettes or myxopapillary patterns. Immunohistochemical staining bolstered this divergence, marking the tumor cells positive for glial fibrillary acidic protein and epithelial membrane antigen with a characteristic ring‐like pattern, and CD99 but negative for Olig‐2. These markers, alongside methylation profiling, facilitated its classification as a myxopapillary ependymoma (MPE), despite the atypical histologic features. This profile underscores the necessity of a multifaceted diagnostic process, especially when histological presentation is uncommon, confirming the critical role of immunohistochemistry and molecular diagnostics in classifying morphologically ambiguous ependymomas and exemplifying the histological diversity within MPEs. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Prediction of brain metastasis development with DNA methylation signatures.

Author

Zuccato JA, Mamatjan Y, Nassiri F, Ajisebutu A, Liu JC, Muazzam A, Singh O, Zhang W, Voisin M, Mirhadi S, Suppiah S, Wybenga-Groot L, Tajik A, Simpson C, Saarela O, Tsao MS, Kislinger T, Aldape KD, Moran MF, Patil V, and Zadeh G

Abstract

Brain metastases (BMs) are the most common and among the deadliest brain tumors. Currently, there are no reliable predictors of BM development from primary cancer, which limits early intervention. Lung adenocarcinoma (LUAD) is the most common BM source and here we obtained 402 tumor and plasma samples from a large cohort of patients with LUAD with or without BM (n = 346). LUAD DNA methylation signatures were evaluated to build and validate an accurate model predicting BM development from LUAD, which was integrated with clinical factors to provide comprehensive patient-specific BM risk probabilities in a nomogram. Additionally, immune and cell interaction gene sets were differentially methylated at promoters in BM versus paired primary LUAD and had aligning dysregulation in the proteome. Immune cells were differentially abundant in BM versus LUAD. Finally, liquid biomarkers identified from methylated cell-free DNA sequenced in plasma were used to generate and validate accurate classifiers for early BM detection. Overall, LUAD methylomes can be leveraged to predict and noninvasively identify BM, moving toward improved patient outcomes with personalized treatment., (© 2024. The Author(s).)

Published
2024
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50. Meningioma: International Consortium on Meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients.

Author

Wang JZ, Landry AP, Raleigh DR, Sahm F, Walsh KM, Goldbrunner R, Yefet LS, Tonn JC, Gui C, Ostrom QT, Barnholtz-Sloan J, Perry A, Ellenbogen Y, Hanemann CO, Jungwirth G, Jenkinson MD, Tabatabai G, Mathiesen TI, McDermott MW, Tatagiba M, la Fougère C, Maas SLN, Galldiks N, Albert NL, Brastianos PK, Ehret F, Minniti G, Lamszus K, Ricklefs FL, Schittenhelm J, Drummond KJ, Dunn IF, Pathmanaban ON, Cohen-Gadol AA, Sulman EP, Tabouret E, Le Rhun E, Mawrin C, Moliterno J, Weller M, Bi WL, Gao A, Yip S, Niyazi M, Aldape K, Wen PY, Short S, Preusser M, Nassiri F, and Zadeh G

Subjects
Humans, Consensus, Biomarkers, Tumor, Meningioma therapy, Meningioma pathology, Meningioma diagnosis, Meningioma classification, Meningeal Neoplasms therapy, Meningeal Neoplasms pathology, Meningeal Neoplasms diagnosis, Meningeal Neoplasms classification
Abstract

Meningiomas are the most common primary intracranial tumors in adults and are increasing in incidence due to the aging population and increased access to neuroimaging. While most exhibit nonmalignant behavior, a subset of meningiomas are biologically aggressive and are associated with treatment resistance, resulting in significant neurologic morbidity and even mortality. In recent years, meaningful advances in our understanding of the biology of these tumors have led to the incorporation of molecular biomarkers into their grading and prognostication. However, unlike other central nervous system (CNS) tumors, a unified molecular taxonomy for meningiomas has not yet been established and remains an overarching goal of the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official World Health Organization (cIMPACT-NOW) working group. Additionally, clinical equipoise still remains on how specific meningioma cases and patient populations should be optimally managed. To address these existing gaps, members of the International Consortium on Meningiomas including field-leading experts, have prepared this comprehensive consensus narrative review directed toward clinicians, researchers, and patients. Included in this manuscript are detailed overviews of proposed molecular classifications, novel biomarkers, contemporary treatment strategies, trials on systemic therapies, health-related quality-of-life studies, and management strategies for unique meningioma patient populations. In each section, we discuss the current state of knowledge as well as ongoing clinical and research challenges to road map future directions for further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Published
2024
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