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1. Association of partial T2-FLAIR mismatch sign and isocitrate dehydrogenase mutation in WHO grade 4 gliomas: results from the ReSPOND consortium.

Author

Lee, Matthew, Patel, Sohil, Mohan, Suyash, Akbari, Hamed, Bakas, Spyridon, Nasrallah, MacLean, Calabrese, Evan, Rudie, Jeffrey, LaMontagne, Pamela, Marcus, Daniel, Colen, Rivka, Balana, Carmen, Choi, Yoon, Badve, Chaitra, Barnholtz-Sloan, Jill, Sloan, Andrew, Booth, Thomas, Palmer, Joshua, Dicker, Adam, Flanders, Adam, Shi, Wenyin, Griffith, Brent, Poisson, Laila, Chakravarti, Arnab, Mahajan, Abhishek, Chang, Susan, Orringer, Daniel, Davatzikos, Christos, Jain, Rajan, and Villanueva-Meyer, Javier

Subjects
Astrocytoma, Glioblastoma, Isocitrate dehydrogenase, Magnetic resonance imaging, T2-FLAIR mismatch, Adult, Humans, Isocitrate Dehydrogenase, Brain Neoplasms, Retrospective Studies, Glioma, Magnetic Resonance Imaging, Mutation, World Health Organization
Abstract

PURPOSE: While the T2-FLAIR mismatch sign is highly specific for isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted astrocytomas among lower-grade gliomas, its utility in WHO grade 4 gliomas is not well-studied. We derived the partial T2-FLAIR mismatch sign as an imaging biomarker for IDH mutation in WHO grade 4 gliomas. METHODS: Preoperative MRI scans of adult WHO grade 4 glioma patients (n = 2165) from the multi-institutional ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium were analyzed. Diagnostic performance of the partial T2-FLAIR mismatch sign was evaluated. Subset analyses were performed to assess associations of imaging markers with overall survival (OS). RESULTS: One hundred twenty-one (5.6%) of 2165 grade 4 gliomas were IDH-mutant. Partial T2-FLAIR mismatch was present in 40 (1.8%) cases, 32 of which were IDH-mutant, yielding 26.4% sensitivity, 99.6% specificity, 80.0% positive predictive value, and 95.8% negative predictive value. Multivariate logistic regression demonstrated IDH mutation was significantly associated with partial T2-FLAIR mismatch (odds ratio [OR] 5.715, 95% CI [1.896, 17.221], p = 0.002), younger age (OR 0.911 [0.895, 0.927], p

Published
2023

2. Federated Learning Enables Big Data for Rare Cancer Boundary Detection

Author

Pati, Sarthak, Baid, Ujjwal, Edwards, Brandon, Sheller, Micah, Wang, Shih-Han, Reina, G Anthony, Foley, Patrick, Gruzdev, Alexey, Karkada, Deepthi, Davatzikos, Christos, Sako, Chiharu, Ghodasara, Satyam, Bilello, Michel, Mohan, Suyash, Vollmuth, Philipp, Brugnara, Gianluca, Preetha, Chandrakanth J, Sahm, Felix, Maier-Hein, Klaus, Zenk, Maximilian, Bendszus, Martin, Wick, Wolfgang, Calabrese, Evan, Rudie, Jeffrey, Villanueva-Meyer, Javier, Cha, Soonmee, Ingalhalikar, Madhura, Jadhav, Manali, Pandey, Umang, Saini, Jitender, Garrett, John, Larson, Matthew, Jeraj, Robert, Currie, Stuart, Frood, Russell, Fatania, Kavi, Huang, Raymond Y, Chang, Ken, Balana, Carmen, Capellades, Jaume, Puig, Josep, Trenkler, Johannes, Pichler, Josef, Necker, Georg, Haunschmidt, Andreas, Meckel, Stephan, Shukla, Gaurav, Liem, Spencer, Alexander, Gregory S, Lombardo, Joseph, Palmer, Joshua D, Flanders, Adam E, Dicker, Adam P, Sair, Haris I, Jones, Craig K, Venkataraman, Archana, Jiang, Meirui, So, Tiffany Y, Chen, Cheng, Heng, Pheng Ann, Dou, Qi, Kozubek, Michal, Lux, Filip, Michálek, Jan, Matula, Petr, Keřkovský, Miloš, Kopřivová, Tereza, Dostál, Marek, Vybíhal, Václav, Vogelbaum, Michael A, Mitchell, J Ross, Farinhas, Joaquim, Maldjian, Joseph A, Yogananda, Chandan Ganesh Bangalore, Pinho, Marco C, Reddy, Divya, Holcomb, James, Wagner, Benjamin C, Ellingson, Benjamin M, Cloughesy, Timothy F, Raymond, Catalina, Oughourlian, Talia, Hagiwara, Akifumi, Wang, Chencai, To, Minh-Son, Bhardwaj, Sargam, Chong, Chee, Agzarian, Marc, Falcão, Alexandre Xavier, Martins, Samuel B, Teixeira, Bernardo C A, Sprenger, Flávia, Menotti, David, Lucio, Diego R, LaMontagne, Pamela, Marcus, Daniel, Wiestler, Benedikt, Kofler, Florian, Ezhov, Ivan, Metz, Marie, Jain, Rajan, Lee, Matthew, Lui, Yvonne W, McKinley, Richard, Slotboom, Johannes, Radojewski, Piotr, Meier, Raphael, Wiest, Roland, Murcia, Derrick, Fu, Eric, Haas, Rourke, Thompson, John, Ormond, David Ryan, Badve, Chaitra, Sloan, Andrew E, Vadmal, Vachan, Waite, Kristin, Colen, Rivka R, Pei, Linmin, Ak, Murat, Srinivasan, Ashok, Bapuraj, J Rajiv, Rao, Arvind, Wang, Nicholas, Yoshiaki, Ota, Moritani, Toshio, Turk, Sevcan, Lee, Joonsang, Prabhudesai, Snehal, Morón, Fanny, Mandel, Jacob, Kamnitsas, Konstantinos, Glocker, Ben, Dixon, Luke V M, Williams, Matthew, Zampakis, Peter, Panagiotopoulos, Vasileios, Tsiganos, Panagiotis, Alexiou, Sotiris, Haliassos, Ilias, Zacharaki, Evangelia I, Moustakas, Konstantinos, Kalogeropoulou, Christina, Kardamakis, Dimitrios M, Choi, Yoon Seong, Lee, Seung-Koo, Chang, Jong Hee, Ahn, Sung Soo, Luo, Bing, Poisson, Laila, Wen, Ning, Tiwari, Pallavi, Verma, Ruchika, Bareja, Rohan, Yadav, Ipsa, Chen, Jonathan, Kumar, Neeraj, Smits, Marion, van der Voort, Sebastian R, Alafandi, Ahmed, Incekara, Fatih, Wijnenga, Maarten MJ, Kapsas, Georgios, Gahrmann, Renske, Schouten, Joost W, Dubbink, Hendrikus J, Vincent, Arnaud JPE, Bent, Martin J van den, French, Pim J, Klein, Stefan, Yuan, Yading, Sharma, Sonam, Tseng, Tzu-Chi, Adabi, Saba, Niclou, Simone P, Keunen, Olivier, Hau, Ann-Christin, Vallières, Martin, Fortin, David, Lepage, Martin, Landman, Bennett, Ramadass, Karthik, Xu, Kaiwen, Chotai, Silky, Chambless, Lola B, Mistry, Akshitkumar, Thompson, Reid C, Gusev, Yuriy, Bhuvaneshwar, Krithika, Sayah, Anousheh, Bencheqroun, Camelia, Belouali, Anas, Madhavan, Subha, Booth, Thomas C, Chelliah, Alysha, Modat, Marc, Shuaib, Haris, Dragos, Carmen, Abayazeed, Aly, Kolodziej, Kenneth, Hill, Michael, Abbassy, Ahmed, Gamal, Shady, Mekhaimar, Mahmoud, Qayati, Mohamed, Reyes, Mauricio, Park, Ji Eun, Yun, Jihye, Kim, Ho Sung, Mahajan, Abhishek, Muzi, Mark, Benson, Sean, Beets-Tan, Regina G H, Teuwen, Jonas, Herrera-Trujillo, Alejandro, Trujillo, Maria, Escobar, William, Abello, Ana, Bernal, Jose, Gómez, Jhon, Choi, Joseph, Baek, Stephen, Kim, Yusung, Ismael, Heba, Allen, Bryan, Buatti, John M, Kotrotsou, Aikaterini, Li, Hongwei, Weiss, Tobias, Weller, Michael, Bink, Andrea, Pouymayou, Bertrand, Shaykh, Hassan F, Saltz, Joel, Prasanna, Prateek, Shrestha, Sampurna, Mani, Kartik M, Payne, David, Kurc, Tahsin, Pelaez, Enrique, Franco-Maldonado, Heydy, Loayza, Francis, Quevedo, Sebastian, Guevara, Pamela, Torche, Esteban, Mendoza, Cristobal, Vera, Franco, Ríos, Elvis, López, Eduardo, Velastin, Sergio A, Ogbole, Godwin, Oyekunle, Dotun, Odafe-Oyibotha, Olubunmi, Osobu, Babatunde, Shu'aibu, Mustapha, Dorcas, Adeleye, Soneye, Mayowa, Dako, Farouk, Simpson, Amber L, Hamghalam, Mohammad, Peoples, Jacob J, Hu, Ricky, Tran, Anh, Cutler, Danielle, Moraes, Fabio Y, Boss, Michael A, Gimpel, James, Veettil, Deepak Kattil, Schmidt, Kendall, Bialecki, Brian, Marella, Sailaja, Price, Cynthia, Cimino, Lisa, Apgar, Charles, Shah, Prashant, Menze, Bjoern, Barnholtz-Sloan, Jill S, Martin, Jason, and Bakas, Spyridon

Subjects
Computer Science - Machine Learning, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

Although machine learning (ML) has shown promise in numerous domains, there are concerns about generalizability to out-of-sample data. This is currently addressed by centrally sharing ample, and importantly diverse, data from multiple sites. However, such centralization is challenging to scale (or even not feasible) due to various limitations. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here we present findings from the largest FL study to-date, involving data from 71 healthcare institutions across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, utilizing the largest dataset of such patients ever used in the literature (25,256 MRI scans from 6,314 patients). We demonstrate a 33% improvement over a publicly trained model to delineate the surgically targetable tumor, and 23% improvement over the tumor's entire extent. We anticipate our study to: 1) enable more studies in healthcare informed by large and diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further quantitative analyses for glioblastoma via performance optimization of our consensus model for eventual public release, and 3) demonstrate the effectiveness of FL at such scale and task complexity as a paradigm shift for multi-site collaborations, alleviating the need for data sharing., Comment: federated learning, deep learning, convolutional neural network, segmentation, brain tumor, glioma, glioblastoma, FeTS, BraTS

Published
2022
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3. Glioma progression is shaped by genetic evolution and microenvironment interactions

Author

Varn, Frederick S, Johnson, Kevin C, Martinek, Jan, Huse, Jason T, Nasrallah, MacLean P, Wesseling, Pieter, Cooper, Lee AD, Malta, Tathiane M, Wade, Taylor E, Sabedot, Thais S, Brat, Daniel, Gould, Peter V, Wöehrer, Adelheid, Aldape, Kenneth, Ismail, Azzam, Sivajothi, Santhosh K, Barthel, Floris P, Kim, Hoon, Kocakavuk, Emre, Ahmed, Nazia, White, Kieron, Datta, Indrani, Moon, Hyo-Eun, Pollock, Steven, Goldfarb, Christine, Lee, Ga-Hyun, Garofano, Luciano, Anderson, Kevin J, Nehar-Belaid, Djamel, Barnholtz-Sloan, Jill S, Bakas, Spyridon, Byrne, Annette T, D’Angelo, Fulvio, Gan, Hui K, Khasraw, Mustafa, Migliozzi, Simona, Ormond, D Ryan, Paek, Sun Ha, Van Meir, Erwin G, Walenkamp, Annemiek ME, Watts, Colin, Weiss, Tobias, Weller, Michael, Palucka, Karolina, Stead, Lucy F, Poisson, Laila M, Noushmehr, Houtan, Iavarone, Antonio, Verhaak, Roel GW, Consortium, The GLASS, Alfaro, Kristin D, Amin, Samirkumar B, Ashley, David M, Bock, Christoph, Brodbelt, Andrew, Bulsara, Ketan R, and Castro, Ana Valeria

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Brain Disorders, Brain Cancer, Genetics, Cancer, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Adult, Brain Neoplasms, Evolution, Molecular, Genes, p16, Glioma, Humans, Isocitrate Dehydrogenase, Mutation, Neoplasm Recurrence, Local, Tumor Microenvironment, GLASS Consortium, genomics, glioblastoma, glioma, hypermutation, macrophages, microenvironment, neurons, single-cell, spatial imaging, treatment resistance, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

The factors driving therapy resistance in diffuse glioma remain poorly understood. To identify treatment-associated cellular and genetic changes, we analyzed RNA and/or DNA sequencing data from the temporally separated tumor pairs of 304 adult patients with isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant glioma. Tumors recurred in distinct manners that were dependent on IDH mutation status and attributable to changes in histological feature composition, somatic alterations, and microenvironment interactions. Hypermutation and acquired CDKN2A deletions were associated with an increase in proliferating neoplastic cells at recurrence in both glioma subtypes, reflecting active tumor growth. IDH-wild-type tumors were more invasive at recurrence, and their neoplastic cells exhibited increased expression of neuronal signaling programs that reflected a possible role for neuronal interactions in promoting glioma progression. Mesenchymal transition was associated with the presence of a myeloid cell state defined by specific ligand-receptor interactions with neoplastic cells. Collectively, these recurrence-associated phenotypes represent potential targets to alter disease progression.

Published
2022

4. Development of ‘Core Outcome Sets’ for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings

Author

Millward, Christopher P, Armstrong, Terri S, Barrington, Heather, Bell, Sabrina, Brodbelt, Andrew R, Bulbeck, Helen, Crofton, Anna, Dirven, Linda, Georgious, Theo, Grundy, Paul L, Islim, Abdurrahman I, Javadpour, Mohsen, Keshwara, Sumirat M, Koszdin, Shelli D, Marson, Anthony G, McDermott, Michael W, Meling, Torstein R, Oliver, Kathy, Plaha, Puneet, Preusser, Matthias, Santarius, Thomas, Srikandarajah, Nisaharan, Taphoorn, Martin JB, Turner, Carole, Watts, Colin, Weller, Michael, Williamson, Paula R, Zadeh, Gelareh, Najafabadi, Amir H Zamanipoor, Jenkinson, Michael D, Aldape, Kenneth, Au, Karolyn, Barnhartz-Sloan, Jill, Bi, Wenya Linda, Behling, Felix, Brastianos, Priscilla K, Brodie, Chaya, Butowski, Nicholas, Carlotti, Carlos, Castro, Ana, Cohen-Gadol, Aaron, Couce, Marta, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Dunn, Ian F, Erker, Craig, Felicella, Michelle, Fountain, Daniel M, Galanis, Evanthia, Galldiks, Norbert, Giannini, Caterina, Goldbrunner, Roland, Griffith, Brent, Hashizume, Rintaro, Hanemann, C Oliver, Herold-Mende, Christel, Hnenny, Luke, Horbinski, Craig, Huang, Raymond Y, James, David, Jungk, Christine, Jungwirth, Gerhard, Kaufmann, Timothy J, Krischek, Boris, Kurz, Sylvia, Lachance, Daniel, Lafougère, Christian, Lamszus, Katrin, Lee, Ian, Liu, Jeff C, Makarenko, Serge, Malta, Tathiana, Mamatjan, Yasin, Mansouri, Alireza, Mawrin, Christian, McDermott, Michael, Moliterno-Gunel, Jennifer, Morokoff, Andrew, Munoz, David, Nassiri, Farshad, Noushmehr, Houtan, Ng, Ho-Keung, Perry, Arie, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Ragunathan, Aditya, Raleigh, David, Renovanz, Mirjam, Ricklefs, Franz, Sahm, Felix, Saladino, Andrea, Santacroce, Antonio, Schittenhelm, Jens, and Schichor, Christian

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Neurosciences, Brain Disorders, Clinical Research, Clinical Trials and Supportive Activities, Cancer, Consensus, Delphi Technique, Humans, Meningeal Neoplasms, Meningioma, Research Design, Systematic Reviews as Topic, Treatment Outcome, EORTC BTG, ICOM, EANO, SNO, RANO-PRO, BNOS, SBNS, BIMS, TBTC, International Brain Tumour Alliance, Brainstrust, and Brain Tumour Foundation of Canada, clinical trial, core outcome set, meningioma, Public Health and Health Services, Other Medical and Health Sciences, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508.

Published
2022

6. Detection of diagnostic and prognostic methylation-based signatures in liquid biopsy specimens from patients with meningiomas

Author

Herrgott, Grayson A., Snyder, James M., She, Ruicong, Malta, Tathiane M., Sabedot, Thais S., Lee, Ian Y., Pawloski, Jacob, Podolsky-Gondim, Guilherme G., Asmaro, Karam P., Zhang, Jiaqi, Cannella, Cara E., Nelson, Kevin, Thomas, Bartow, deCarvalho, Ana C., Hasselbach, Laura A., Tundo, Kelly M., Newaz, Rehnuma, Transou, Andrea, Morosini, Natalia, Francisco, Victor, Poisson, Laila M., Chitale, Dhananjay, Mukherjee, Abir, Mosella, Maritza S., Robin, Adam M., Walbert, Tobias, Rosenblum, Mark, Mikkelsen, Tom, Kalkanis, Steven, Tirapelli, Daniela P. C., Weisenberger, Daniel J., Carlotti, Jr, Carlos G., Rock, Jack, Castro, Ana Valeria, and Noushmehr, Houtan

Published
2023
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7. Author Correction: Federated learning enables big data for rare cancer boundary detection

Author

Pati, Sarthak, Baid, Ujjwal, Edwards, Brandon, Sheller, Micah, Wang, Shih-Han, Reina, G. Anthony, Foley, Patrick, Gruzdev, Alexey, Karkada, Deepthi, Davatzikos, Christos, Sako, Chiharu, Ghodasara, Satyam, Bilello, Michel, Mohan, Suyash, Vollmuth, Philipp, Brugnara, Gianluca, Preetha, Chandrakanth J., Sahm, Felix, Maier-Hein, Klaus, Zenk, Maximilian, Bendszus, Martin, Wick, Wolfgang, Calabrese, Evan, Rudie, Jeffrey, Villanueva-Meyer, Javier, Cha, Soonmee, Ingalhalikar, Madhura, Jadhav, Manali, Pandey, Umang, Saini, Jitender, Garrett, John, Larson, Matthew, Jeraj, Robert, Currie, Stuart, Frood, Russell, Fatania, Kavi, Huang, Raymond Y., Chang, Ken, Balaña, Carmen, Capellades, Jaume, Puig, Josep, Trenkler, Johannes, Pichler, Josef, Necker, Georg, Haunschmidt, Andreas, Meckel, Stephan, Shukla, Gaurav, Liem, Spencer, Alexander, Gregory S., Lombardo, Joseph, Palmer, Joshua D., Flanders, Adam E., Dicker, Adam P., Sair, Haris I., Jones, Craig K., Venkataraman, Archana, Jiang, Meirui, So, Tiffany Y., Chen, Cheng, Heng, Pheng Ann, Dou, Qi, Kozubek, Michal, Lux, Filip, Michálek, Jan, Matula, Petr, Keřkovský, Miloš, Kopřivová, Tereza, Dostál, Marek, Vybíhal, Václav, Vogelbaum, Michael A., Mitchell, J. Ross, Farinhas, Joaquim, Maldjian, Joseph A., Yogananda, Chandan Ganesh Bangalore, Pinho, Marco C., Reddy, Divya, Holcomb, James, Wagner, Benjamin C., Ellingson, Benjamin M., Cloughesy, Timothy F., Raymond, Catalina, Oughourlian, Talia, Hagiwara, Akifumi, Wang, Chencai, To, Minh-Son, Bhardwaj, Sargam, Chong, Chee, Agzarian, Marc, Falcão, Alexandre Xavier, Martins, Samuel B., Teixeira, Bernardo C. A., Sprenger, Flávia, Menotti, David, Lucio, Diego R., LaMontagne, Pamela, Marcus, Daniel, Wiestler, Benedikt, Kofler, Florian, Ezhov, Ivan, Metz, Marie, Jain, Rajan, Lee, Matthew, Lui, Yvonne W., McKinley, Richard, Slotboom, Johannes, Radojewski, Piotr, Meier, Raphael, Wiest, Roland, Murcia, Derrick, Fu, Eric, Haas, Rourke, Thompson, John, Ormond, David Ryan, Badve, Chaitra, Sloan, Andrew E., Vadmal, Vachan, Waite, Kristin, Colen, Rivka R., Pei, Linmin, Ak, Murat, Srinivasan, Ashok, Bapuraj, J. Rajiv, Rao, Arvind, Wang, Nicholas, Yoshiaki, Ota, Moritani, Toshio, Turk, Sevcan, Lee, Joonsang, Prabhudesai, Snehal, Morón, Fanny, Mandel, Jacob, Kamnitsas, Konstantinos, Glocker, Ben, Dixon, Luke V. M., Williams, Matthew, Zampakis, Peter, Panagiotopoulos, Vasileios, Tsiganos, Panagiotis, Alexiou, Sotiris, Haliassos, Ilias, Zacharaki, Evangelia I., Moustakas, Konstantinos, Kalogeropoulou, Christina, Kardamakis, Dimitrios M., Choi, Yoon Seong, Lee, Seung-Koo, Chang, Jong Hee, Ahn, Sung Soo, Luo, Bing, Poisson, Laila, Wen, Ning, Tiwari, Pallavi, Verma, Ruchika, Bareja, Rohan, Yadav, Ipsa, Chen, Jonathan, Kumar, Neeraj, Smits, Marion, van der Voort, Sebastian R., Alafandi, Ahmed, Incekara, Fatih, Wijnenga, Maarten M. J., Kapsas, Georgios, Gahrmann, Renske, Schouten, Joost W., Dubbink, Hendrikus J., Vincent, Arnaud J. P. E., van den Bent, Martin J., French, Pim J., Klein, Stefan, Yuan, Yading, Sharma, Sonam, Tseng, Tzu-Chi, Adabi, Saba, Niclou, Simone P., Keunen, Olivier, Hau, Ann-Christin, Vallières, Martin, Fortin, David, Lepage, Martin, Landman, Bennett, Ramadass, Karthik, Xu, Kaiwen, Chotai, Silky, Chambless, Lola B., Mistry, Akshitkumar, Thompson, Reid C., Gusev, Yuriy, Bhuvaneshwar, Krithika, Sayah, Anousheh, Bencheqroun, Camelia, Belouali, Anas, Madhavan, Subha, Booth, Thomas C., Chelliah, Alysha, Modat, Marc, Shuaib, Haris, Dragos, Carmen, Abayazeed, Aly, Kolodziej, Kenneth, Hill, Michael, Abbassy, Ahmed, Gamal, Shady, Mekhaimar, Mahmoud, Qayati, Mohamed, Reyes, Mauricio, Park, Ji Eun, Yun, Jihye, Kim, Ho Sung, Mahajan, Abhishek, Muzi, Mark, Benson, Sean, Beets-Tan, Regina G. H., Teuwen, Jonas, Herrera-Trujillo, Alejandro, Trujillo, Maria, Escobar, William, Abello, Ana, Bernal, Jose, Gómez, Jhon, Choi, Joseph, Baek, Stephen, Kim, Yusung, Ismael, Heba, Allen, Bryan, Buatti, John M., Kotrotsou, Aikaterini, Li, Hongwei, Weiss, Tobias, Weller, Michael, Bink, Andrea, Pouymayou, Bertrand, Shaykh, Hassan F., Saltz, Joel, Prasanna, Prateek, Shrestha, Sampurna, Mani, Kartik M., Payne, David, Kurc, Tahsin, Pelaez, Enrique, Franco-Maldonado, Heydy, Loayza, Francis, Quevedo, Sebastian, Guevara, Pamela, Torche, Esteban, Mendoza, Cristobal, Vera, Franco, Ríos, Elvis, López, Eduardo, Velastin, Sergio A., Ogbole, Godwin, Soneye, Mayowa, Oyekunle, Dotun, Odafe-Oyibotha, Olubunmi, Osobu, Babatunde, Shu’aibu, Mustapha, Dorcas, Adeleye, Dako, Farouk, Simpson, Amber L., Hamghalam, Mohammad, Peoples, Jacob J., Hu, Ricky, Tran, Anh, Cutler, Danielle, Moraes, Fabio Y., Boss, Michael A., Gimpel, James, Veettil, Deepak Kattil, Schmidt, Kendall, Bialecki, Brian, Marella, Sailaja, Price, Cynthia, Cimino, Lisa, Apgar, Charles, Shah, Prashant, Menze, Bjoern, Barnholtz-Sloan, Jill S., Martin, Jason, and Bakas, Spyridon

Published
2023
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9. Longitudinal molecular trajectories of diffuse glioma in adults

Author

Barthel, Floris P, Johnson, Kevin C, Varn, Frederick S, Moskalik, Anzhela D, Tanner, Georgette, Kocakavuk, Emre, Anderson, Kevin J, Abiola, Olajide, Aldape, Kenneth, Alfaro, Kristin D, Alpar, Donat, Amin, Samirkumar B, Ashley, David M, Bandopadhayay, Pratiti, Barnholtz-Sloan, Jill S, Beroukhim, Rameen, Bock, Christoph, Brastianos, Priscilla K, Brat, Daniel J, Brodbelt, Andrew R, Bruns, Alexander F, Bulsara, Ketan R, Chakrabarty, Aruna, Chakravarti, Arnab, Chuang, Jeffrey H, Claus, Elizabeth B, Cochran, Elizabeth J, Connelly, Jennifer, Costello, Joseph F, Finocchiaro, Gaetano, Fletcher, Michael N, French, Pim J, Gan, Hui K, Gilbert, Mark R, Gould, Peter V, Grimmer, Matthew R, Iavarone, Antonio, Ismail, Azzam, Jenkinson, Michael D, Khasraw, Mustafa, Kim, Hoon, Kouwenhoven, Mathilde CM, LaViolette, Peter S, Li, Meihong, Lichter, Peter, Ligon, Keith L, Lowman, Allison K, Malta, Tathiane M, Mazor, Tali, McDonald, Kerrie L, Molinaro, Annette M, Nam, Do-Hyun, Nayyar, Naema, Ng, Ho Keung, Ngan, Chew Yee, Niclou, Simone P, Niers, Johanna M, Noushmehr, Houtan, Noorbakhsh, Javad, Ormond, D Ryan, Park, Chul-Kee, Poisson, Laila M, Rabadan, Raul, Radlwimmer, Bernhard, Rao, Ganesh, Reifenberger, Guido, Sa, Jason K, Schuster, Michael, Shaw, Brian L, Short, Susan C, Smitt, Peter A Sillevis, Sloan, Andrew E, Smits, Marion, Suzuki, Hiromichi, Tabatabai, Ghazaleh, Van Meir, Erwin G, Watts, Colin, Weller, Michael, Wesseling, Pieter, Westerman, Bart A, Widhalm, Georg, Woehrer, Adelheid, Yung, WK Alfred, Zadeh, Gelareh, Huse, Jason T, De Groot, John F, Stead, Lucy F, and Verhaak, Roel GW

Subjects
Neurosciences, Brain Disorders, Cancer, Rare Diseases, Brain Cancer, Genetics, Adult, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Disease Progression, Glioma, Humans, Isocitrate Dehydrogenase, Mutation, Polymorphism, Single Nucleotide, Recurrence, GLASS Consortium, General Science & Technology
Abstract

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear1,2. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.

Published
2019

10. A guide to successful management of collaborative partnerships in quantitative research: An illustration of the science of team science

Author

Platt, Alyssa, primary, Truong, Tracy, additional, Boulos, Mary, additional, Carlson, Nichole E., additional, Desai, Manisha, additional, Elam, Monica M., additional, Slade, Emily, additional, Hanlon, Alexandra L., additional, Hurst, Jillian H., additional, Olsen, Maren K., additional, Poisson, Laila M., additional, Rende, Lacey, additional, and Pomann, Gina‐Maria, additional

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2024
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11. 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

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2024
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12. 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

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2024
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13. 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

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2024
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14. 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

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2024
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15. 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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16. Imaging and diagnostic advances for intracranial meningiomas.

Author

Huang, Raymond Y, Bi, Wenya Linda, Griffith, Brent, Kaufmann, Timothy J, la Fougère, Christian, Schmidt, Nils Ole, Tonn, Jöerg C, Vogelbaum, Michael A, Wen, Patrick Y, Aldape, Kenneth, Nassiri, Farshad, Zadeh, Gelareh, Dunn, Ian F, Au, Karolyn, Barnhartz-Sloan, Jill, Brastianos, Priscilla K, Butowski, Nicholas, Carlotti, Carlos, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Galanis, Evanthia, Giannini, Caterina, Goldbrunner, Roland, Hashizume, Rintaro, Hanemann, C Oliver, Herold-Mende, Christel, Horbinski, Craig, James, David, Jenkinson, Michael D, Jungk, Christine, Kaufman, Timothy J, Krischek, Boris, Lachance, Daniel, Lafougère, Christian, Lee, Ian, Liu, Jeff C, Mamatjan, Yasin, Mansouri, Alireza, Mawrin, Christian, McDermott, Michael, Munoz, David, Noushmehr, Houtan, Ng, Ho-Keung, Perry, Arie, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Raleigh, David, Sahm, Felix, Saladino, Andrea, Santarius, Thomas, Schichor, Christian, Schultz, David, Schmidt, Nils O, Selman, Warren, Sloan, Andrew, Spears, Julian, Snyder, James, Suppiah, Suganth, Tabatabai, Ghazaleh, Tatagiba, Marcos, Tirapelli, Daniela, Tonn, Joerg C, Tsang, Derek, Deimling, Andreas von, Walbert, Tobias, Westphal, Manfred, and Workewych, Adriana M

Subjects
Rare Diseases, Neurosciences, Brain Disorders, Biomedical Imaging, Cancer, Brain Cancer, Humans, Meningeal Neoplasms, Meningioma, Multimodal Imaging, Neuroimaging, International Consortium on Meningiomas, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

The archetypal imaging characteristics of meningiomas are among the most stereotypic of all central nervous system (CNS) tumors. In the era of plain film and ventriculography, imaging was only performed if a mass was suspected, and their results were more suggestive than definitive. Following more than a century of technological development, we can now rely on imaging to non-invasively diagnose meningioma with great confidence and precisely delineate the locations of these tumors relative to their surrounding structures to inform treatment planning. Asymptomatic meningiomas may be identified and their growth monitored over time; moreover, imaging routinely serves as an essential tool to survey tumor burden at various stages during the course of treatment, thereby providing guidance on their effectiveness or the need for further intervention. Modern radiological techniques are expanding the power of imaging from tumor detection and monitoring to include extraction of biologic information from advanced analysis of radiological parameters. These contemporary approaches have led to promising attempts to predict tumor grade and, in turn, contribute prognostic data. In this supplement article, we review important current and future aspects of imaging in the diagnosis and management of meningioma, including conventional and advanced imaging techniques using CT, MRI, and nuclear medicine.

Published
2019

17. Molecular and translational advances in meningiomas

Author

Suppiah, Suganth, Nassiri, Farshad, Bi, Wenya Linda, Dunn, Ian F, Hanemann, Clemens Oliver, Horbinski, Craig M, Hashizume, Rintaro, James, Charles David, Mawrin, Christian, Noushmehr, Houtan, Perry, Arie, Sahm, Felix, Sloan, Andrew, Von Deimling, Andreas, Wen, Patrick Y, Aldape, Kenneth, Zadeh, Gelareh, Au, Karolyn, Barnhartz-Sloan, Jill, Brastianos, Priscilla K, Butowski, Nicholas, Carlotti, Carlos, Cusimano, Michael D, DiMeco, Francesco, Drummond, Katharine, Galanis, Evanthia, Giannini, Caterina, Goldbrunner, Roland, Griffith, Brent, Hanemann, C Oliver, Herold-Mende, Christel, Horbinski, Craig, Huang, Raymond Y, James, David, Jenkinson, Michael D, Jungk, Christine, Kaufman, Timothy J, Krischek, Boris, Lachance, Daniel, Lafougère, Christian, Lee, Ian, Liu, Jeff C, Mamatjan, Yasin, Mansouri, Alireza, McDermott, Michael, Munoz, David, Ng, Ho-Keung, Pirouzmand, Farhad, Poisson, Laila M, Pollo, Bianca, Raleigh, David, Saladino, Andrea, Santarius, Thomas, Schichor, Christian, Schultz, David, Schmidt, Nils O, Selman, Warren, Spears, Julian, Snyder, James, Tabatabai, Ghazaleh, Tatagiba, Marcos, Tirapelli, Daniela, Tonn, Joerg C, Tsang, Derek, Vogelbaum, Michael A, Deimling, Andreas von, Walbert, Tobias, Westphal, Manfred, and Workewych, Adriana M

Subjects
Brain Cancer, Cancer, Brain Disorders, Rare Diseases, Human Genome, Genetics, Combined Modality Therapy, Genomics, Humans, Meningeal Neoplasms, Meningioma, Molecular Targeted Therapy, Prognosis, Translational Research, Biomedical, biomolecular, cell lines, epigenetic, genetic, sporadic meningioma, xenograft, International Consortium on Meningiomas, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Meningiomas are the most common primary intracranial neoplasm. The current World Health Organization (WHO) classification categorizes meningiomas based on histopathological features, but emerging molecular data demonstrate the importance of genomic and epigenomic factors in the clinical behavior of these tumors. Treatment options for symptomatic meningiomas are limited to surgical resection where possible and adjuvant radiation therapy for tumors with concerning histopathological features or recurrent disease. At present, alternative adjuvant treatment options are not available in part due to limited historical biological analysis and clinical trial investigation on meningiomas. With advances in molecular and genomic techniques in the last decade, we have witnessed a surge of interest in understanding the genomic and epigenomic landscape of meningiomas. The field is now at the stage to adopt this molecular knowledge to refine meningioma classification and introduce molecular algorithms that can guide prediction and therapeutics for this tumor type. Animal models that recapitulate meningiomas faithfully are in critical need to test new therapeutics to facilitate rapid-cycle translation to clinical trials. Here we review the most up-to-date knowledge of molecular alterations that provide insight into meningioma behavior and are ready for application to clinical trial investigation, and highlight the landscape of available preclinical models in meningiomas.

Published
2019

20. Utility of an Untargeted Metabolomics Approach Using a 2D GC-GC-MS Platform to Distinguish Relapsing and Progressive Multiple Sclerosis.

Author

Datta, Indrani, Zahoor, Insha, Ata, Nasar, Rashid, Faraz, Cerghet, Mirela, Rattan, Ramandeep, Poisson, Laila M., and Giri, Shailendra

Subjects
METABOLOMIC fingerprinting, CENTRAL nervous system diseases, REGULATOR genes, MULTIPLE sclerosis, YOUNG adults, INTEGRINS
Abstract

Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease of the central nervous system (CNS) in young adults and results in progressive neurological defects. The relapsing-remitting phenotype (RRMS) is the most common disease course in MS, which ultimately progresses to secondary progressive MS (SPMS), while primary progressive MS (PPMS) is a type of MS that worsens gradually over time without remissions. There is a gap in knowledge regarding whether the relapsing form can be distinguished from the progressive course, or healthy subjects (HS) based on an altered serum metabolite profile. In this study, we performed global untargeted metabolomics with the 2D GC-GC-MS platform to identify altered metabolites between RRMS, PPMS, and HS. We profiled 235 metabolites in the serum of patients with RRMS (n = 41), PPMS (n = 31), and HS (n = 91). A comparison of RRMS and HS patients revealed 22 significantly altered metabolites at p < 0.05 (false-discovery rate [FDR] = 0.3). The PPMS and HS comparisons revealed 28 altered metabolites at p < 0.05 (FDR = 0.2). Pathway analysis using MetaboAnalyst revealed enrichment of four metabolic pathways in both RRMS and PPMS (hypergeometric test p < 0.05): (1) galactose metabolism; (2) amino sugar and nucleotide sugar metabolism; (3) phenylalanine, tyrosine, and tryptophan biosynthesis; and (4) aminoacyl-tRNA biosynthesis. The Qiagen IPA enrichment test identified the sulfatase 2 (SULF2) (p = 0.0033) and integrin subunit beta 1 binding protein 1 (ITGB1BP1) (p = 0.0067) genes as upstream regulators of altered metabolites in the RRMS vs. HS groups. However, in the PPMS vs. HS comparison, valine was enriched in the neurodegeneration of brain cells (p = 0.05), and heptadecanoic acid, alpha-ketoisocaproic acid, and glycerol participated in inflammation in the CNS (p = 0.03). Overall, our study suggests that RRMS and PPMS may contribute metabolic fingerprints in the form of unique altered metabolites for discriminating MS disease from HS, with the potential for constructing a metabolite panel for progressive autoimmune diseases such as MS. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Glioma through the looking GLASS: molecular evolution of diffuse gliomas and the Glioma Longitudinal Analysis Consortium

Author

Aldape, Kenneth, Amin, Samirkumar B, Ashley, David M, Barnholtz-Sloan, Jill S, Bates, Amanda J, Beroukhim, Rameen, Bock, Christoph, Brat, Daniel J, Claus, Elizabeth B, Costello, Joseph F, de Groot, John F, Finocchiaro, Gaetano, French, Pim J, Gan, Hui K, Griffith, Brent, Herold-Mende, Christel C, Horbinski, Craig, Iavarone, Antonio, Kalkanis, Steven N, Karabatsou, Konstantina, Kim, Hoon, Kouwenhoven, Mathilde CM, McDonald, Kerrie L, Miletic, Hrvoje, Nam, Do-Hyun, Ng, Ho Keung, Niclou, Simone P, Noushmehr, Houtan, Ormond, D Ryan, Poisson, Laila M, Reifenberger, Guido, Roncaroli, Federico, Sa, Jason K, Smitt, Peter AE Sillevis, Smits, Marion, Souza, Camila F, Tabatabai, Ghazaleh, Van Meir, Erwin G, Verhaak, Roel GW, Watts, Colin, Wesseling, Pieter, Woehrer, Adelheid, Yung, WK Alfred, Jungk, Christine, Hau, Ann-Christin, van Dyck, Eric, Westerman, Bart A, Yin, Julia, Abiola, Olajide, Zeps, Nikolaj, Grimmond, Sean, Buckland, Michael, Khasraw, Mustafa, Sulman, Erik P, Muscat, Andrea M, and Stead, Lucy

Subjects
Cancer, Human Genome, Brain Cancer, Rare Diseases, Orphan Drug, Brain Disorders, Neurosciences, Genetics, Brain Neoplasms, Evolution, Molecular, Genomics, Glioma, Humans, Longitudinal Studies, characterization, evolution, glioma, sequencing, subtypes, GLASS Consortium, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Adult diffuse gliomas are a diverse group of brain neoplasms that inflict a high emotional toll on patients and their families. The Cancer Genome Atlas and similar projects have provided a comprehensive understanding of the somatic alterations and molecular subtypes of glioma at diagnosis. However, gliomas undergo significant cellular and molecular evolution during disease progression. We review the current knowledge on the genomic and epigenetic abnormalities in primary tumors and after disease recurrence, highlight the gaps in the literature, and elaborate on the need for a new multi-institutional effort to bridge these knowledge gaps and how the Glioma Longitudinal Analysis Consortium (GLASS) aims to systemically catalog the longitudinal changes in gliomas. The GLASS initiative will provide essential insights into the evolution of glioma toward a lethal phenotype, with the potential to reveal targetable vulnerabilities and, ultimately, improved outcomes for a patient population in need.

Published
2018

23. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation

Author

Malta, Tathiane M, Sokolov, Artem, Gentles, Andrew J, Burzykowski, Tomasz, Poisson, Laila, Weinstein, John N, Kamińska, Bożena, Huelsken, Joerg, Omberg, Larsson, Gevaert, Olivier, Colaprico, Antonio, Czerwińska, Patrycja, Mazurek, Sylwia, Mishra, Lopa, Heyn, Holger, Krasnitz, Alex, Godwin, Andrew K, Lazar, Alexander J, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Thorsson, Vesteinn, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G, Ochoa, Angelica, Phillips, Sarah M, Reznik, Ed, and Sanchez-Vega, Francisco

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer Genomics, Rare Diseases, Human Genome, Cancer, Stem Cell Research, Stem Cell Research - Nonembryonic - Human, Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research - Induced Pluripotent Stem Cell, Genetics, Machine Learning and Artificial Intelligence, Good Health and Well Being, Carcinogenesis, Cell Dedifferentiation, DNA Methylation, Databases, Genetic, Epigenesis, Genetic, Humans, Machine Learning, MicroRNAs, Neoplasm Metastasis, Neoplasms, Stem Cells, Transcriptome, Tumor Microenvironment, Cancer Genome Atlas Research Network, The Cancer Genome Atlas, cancer stem cells, dedifferentiation, epigenomic, genomic, machine learning, pan-cancer, stemness, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation.

Published
2018

24. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

Author

Liu, Jianfang, Lichtenberg, Tara, Hoadley, Katherine A, Poisson, Laila M, Lazar, Alexander J, Cherniack, Andrew D, Kovatich, Albert J, Benz, Christopher C, Levine, Douglas A, Lee, Adrian V, Omberg, Larsson, Wolf, Denise M, Shriver, Craig D, Thorsson, Vesteinn, Network, The Cancer Genome Atlas Research, Caesar-Johnson, Samantha J, Demchok, John A, Felau, Ina, Kasapi, Melpomeni, Ferguson, Martin L, Hutter, Carolyn M, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Zhang, Jiashan, Chudamani, Sudha, Liu, Jia, Lolla, Laxmi, Naresh, Rashi, Pihl, Todd, Sun, Qiang, Wan, Yunhu, Wu, Ye, Cho, Juok, DeFreitas, Timothy, Frazer, Scott, Gehlenborg, Nils, Getz, Gad, Heiman, David I, Kim, Jaegil, Lawrence, Michael S, Lin, Pei, Meier, Sam, Noble, Michael S, Saksena, Gordon, Voet, Doug, Zhang, Hailei, Bernard, Brady, Chambwe, Nyasha, Dhankani, Varsha, Knijnenburg, Theo, Kramer, Roger, Leinonen, Kalle, Liu, Yuexin, Miller, Michael, Reynolds, Sheila, Shmulevich, Ilya, Zhang, Wei, Akbani, Rehan, Broom, Bradley M, Hegde, Apurva M, Ju, Zhenlin, Kanchi, Rupa S, Korkut, Anil, Li, Jun, Liang, Han, Ling, Shiyun, Liu, Wenbin, Lu, Yiling, Mills, Gordon B, Ng, Kwok-Shing, Rao, Arvind, Ryan, Michael, Wang, Jing, Weinstein, John N, Zhang, Jiexin, Abeshouse, Adam, Armenia, Joshua, Chakravarty, Debyani, Chatila, Walid K, de Bruijn, Ino, Gao, Jianjiong, Gross, Benjamin E, Heins, Zachary J, Kundra, Ritika, La, Konnor, Ladanyi, Marc, Luna, Augustin, Nissan, Moriah G, Ochoa, Angelica, Phillips, Sarah M, Reznik, Ed, Sanchez-Vega, Francisco, Sander, Chris, Schultz, Nikolaus, Sheridan, Robert, and Sumer, S Onur

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Human Genome, Genetics, Cancer Genomics, Women's Health, Networking and Information Technology R&D (NITRD), Cancer, Biotechnology, Precision Medicine, Good Health and Well Being, Databases, Genetic, Genomics, Humans, Kaplan-Meier Estimate, Neoplasms, Proportional Hazards Models, Cancer Genome Atlas Research Network, Cox proportional hazards regression model, TCGA, The Cancer Genome Atlas, clinical data resource, disease-free interval, disease-specific survival, follow-up time, overall survival, progression-free interval, translational research, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale.

Published
2018

25. The TSHS Resources Portal: A Source of Real and Relevant Data for Teaching Statistics in the Health Sciences

Author

Brearley, Ann M, Bigelow, Carol, Poisson, Laila M, Grambow, Steven C, and Nowacki, Amy S

Subjects
Statistics education, biostatistics education, teaching resource.
Abstract

The use of real and relevant data in the statistics classroom is an ideal for many teachers of statistics, as these offer clear benefits for engagement with the kinds of real world applications that students will encounter in the future. Yet, the time required to identify and obtain well-documented data and to prepare classroom teaching materials is often prohibitive. In this paper we review the many benefits of using real and relevant data, and use these to define the characteristics of a well-documented health sciences data resource. We review the barriers to using real and relevant data in teaching. Lastly, we introduce the Teaching of Statistics in the Health Sciences (TSHS) Resources Portal (https://www.causeweb.org/tshs/), a source for well-documented health-related datasets and teaching materials. This dynamic resource provides a means to both obtain and contribute peer-reviewed educational materials. The target audience of the tool is teachers of statistics in health sciences settings, particularly those who teach introductory and applied courses in the graduate or post-graduate setting, but we expect that other statistics educators seeking rich, well-documented datasets will also find the Portal a useful resource.

Published
2018

27. Impact of genomic background and developmental state on signaling pathways and response to therapy in glioblastoma patient-derived cells

Author

Berezovsky, Artem, primary, Nuga, Oluwademilade, additional, Datta, Indrani, additional, Bergman, Kimberly, additional, Sabedot, Thais, additional, Gurdziel, Katherine, additional, Irtenkauf, Susan, additional, Hasselbach, Laura, additional, Meng, Yuling, additional, Mueller, Claudius, additional, Petricoin, Emanuel F., additional, Brown, Stephen, additional, Purandare, Neeraja, additional, Aras, Sidhesh, additional, Mikkelsen, Tom, additional, Poisson, Laila, additional, Noushmehr, Houtan, additional, Ruden, Douglas, additional, and deCarvalho, Ana C., additional

Published
2024
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30. 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

31. Blood-based targeted metabolipidomics reveals altered omega fatty acid-derived lipid mediators in relapsing-remitting multiple sclerosis patients

Author

Zahoor, Insha, primary, Waters, Jeffrey, additional, Ata, Nasar, additional, Datta, Indrani, additional, Pedersen, Theresa L., additional, Cerghet, Mirela, additional, Poisson, Laila, additional, Markovic-Plese, Silva, additional, Rattan, Ramandeep, additional, Taha, Ameer Y., additional, Newman, John W., additional, and Giri, Shailendra, additional

Published
2024
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32. Molecular Profiling Reveals Biologically Discrete Subsets and Pathways of Progression in Diffuse Glioma

Author

Ceccarelli, Michele, Barthel, Floris P, Malta, Tathiane M, Sabedot, Thais S, Salama, Sofie R, Murray, Bradley A, Morozova, Olena, Newton, Yulia, Radenbaugh, Amie, Pagnotta, Stefano M, Anjum, Samreen, Wang, Jiguang, Manyam, Ganiraju, Zoppoli, Pietro, Ling, Shiyun, Rao, Arjun A, Grifford, Mia, Cherniack, Andrew D, Zhang, Hailei, Poisson, Laila, Carlotti, Carlos Gilberto, da Cunha Tirapelli, Daniela Pretti, Rao, Arvind, Mikkelsen, Tom, Lau, Ching C, Yung, WK Alfred, Rabadan, Raul, Huse, Jason, Brat, Daniel J, Lehman, Norman L, Barnholtz-Sloan, Jill S, Zheng, Siyuan, Hess, Kenneth, Rao, Ganesh, Meyerson, Matthew, Beroukhim, Rameen, Cooper, Lee, Akbani, Rehan, Wrensch, Margaret, Haussler, David, Aldape, Kenneth D, Laird, Peter W, Gutmann, David H, Network, TCGA Research, Arachchi, Harindra, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Barnett, Gene, Baylin, Stephen, Bell, Sue, Benz, Christopher, Bir, Natalie, Black, Keith L, Bodenheimer, Tom, Boice, Lori, Bootwalla, Moiz S, Bowen, Jay, Bristow, Christopher A, Butterfield, Yaron SN, Chen, Qing-Rong, Chin, Lynda, Cho, Juok, Chuah, Eric, Chudamani, Sudha, Coetzee, Simon G, Cohen, Mark L, Colman, Howard, Couce, Marta, D’Angelo, Fulvio, Davidsen, Tanja, Davis, Amy, Demchok, John A, Devine, Karen, Ding, Li, Duell, Rebecca, Elder, J Bradley, Eschbacher, Jennifer M, Fehrenbach, Ashley, Ferguson, Martin, Frazer, Scott, Fuller, Gregory, Fulop, Jordonna, Gabriel, Stacey B, Garofano, Luciano, Gastier-Foster, Julie M, Gehlenborg, Nils, Gerken, Mark, Getz, Gad, Giannini, Caterina, Gibson, William J, Hadjipanayis, Angela, Hayes, D Neil, Heiman, David I, Hermes, Beth, Hilty, Joe, Hoadley, Katherine A, Hoyle, Alan P, and Huang, Mei

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Bioinformatics and Computational Biology, Genetics, Oncology and Carcinogenesis, Orphan Drug, Brain Cancer, Brain Disorders, Biotechnology, Human Genome, Rare Diseases, Neurosciences, Cancer, Adult, Brain Neoplasms, Cell Proliferation, Cluster Analysis, DNA Helicases, DNA Methylation, Epigenesis, Genetic, Glioma, Humans, Isocitrate Dehydrogenase, Middle Aged, Mutation, Nuclear Proteins, Promoter Regions, Genetic, Signal Transduction, Telomerase, Telomere, Transcriptome, X-linked Nuclear Protein, TCGA Research Network, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular correlations, and provide insights into the progression from low- to high-grade disease. Whole-genome sequencing data analysis determined that ATRX but not TERT promoter mutations are associated with increased telomere length. Recent advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitulated through analysis of DNA methylation profiles, which identified clinically relevant molecular subsets. A subtype of IDH mutant glioma was associated with DNA demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity to pilocytic astrocytoma and relatively favorable survival. Understanding of cohesive disease groups may aid improved clinical outcomes.

Published
2016

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

Author

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

Published
2023
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34. NIMG-13. ROBUSTNESS OF PROGNOSTIC STRATIFICATION IN DE NOVO GLIOBLASTOMA PATIENTS ACROSS 22 GEOGRAPHICALLY DISTINCT INSTITUTIONS: INSIGHTS FROM THE RESPOND CONSORTIUM

Author

Akbari, Hamed, primary, Bakas, Spyridon, additional, Garcia, Jose, additional, Kazerooni, Anahita Fathi, additional, Sako, Chiharu, additional, Villanueva-Meyer, Javier, additional, Baid, Ujjwal, additional, Mamourian, Elizabeth, additional, Brem, Steven, additional, Lustig, Robert A, additional, Nasrallah, MacLean P, additional, O'Rourke, Donald M, additional, Calabrese, Evan, additional, Rudie, Jeffrey, additional, Chang, Susan, additional, Rauschecker, Andreas, additional, LaMontagne, Pamela, additional, Marcus, Daniel S, additional, Balana, Carmen, additional, Capellades, Jaume, additional, Puig, Josep, additional, Barnholtz-Sloan, Jill, additional, Badve, Chaitra, additional, Sloan, Andrew, additional, Waite, Kristin, additional, Colen, Rivka, additional, Choi, Yoon Seong, additional, Ahn, Sung Soo, additional, Dicker, Adam P, additional, Flanders, Adam E, additional, Shi, Wenyin, additional, Griffith, Brent, additional, Poisson, Laila M, additional, Rogers, Lisa R, additional, Booth, Thomas C, additional, Jain, Rajan, additional, Chakravarti, Arnab, additional, Palmer, Joshua, additional, Cepeda, Santiago, additional, Wiestler, Benedikt, additional, Stefano, Anna Luisa Di, additional, Alexander, Kimberley, additional, Melhem, Elias R, additional, Woodworth, Graeme F, additional, Kamel, Peter I, additional, Tiwari, Pallavi, additional, Aboian, Mariam, additional, Mohan, Suyash, additional, and Davatzikos, Christos, additional

Published
2023
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35. EPID-15. SEX-SPECIFIC DIFFERENCES IN GLIOBLASTOMA IN THE RESPOND CONSORTIUM

Author

Gongala, Sree, primary, Garcia, Jose, additional, Korakavi, Nisha, additional, Patil, Nirav, additional, Akbari, Hamed, additional, Tippareddy, Charit, additional, Sloan, Andrew, additional, Barnholtz-Sloan, Jill, additional, Bakas, Spyridon, additional, Kazerooni, Anahita Fathi, additional, Sako, Chiharu, additional, Baid, Ujjwal, additional, Brem, Steven, additional, Lustig, Robert A, additional, Capellades, Jaume, additional, Nasrallah, MacLean, additional, O'Rourke, Donald M, additional, LaMontagne, Pamela, additional, Marcus, Daniel S, additional, Balana, Carmen, additional, Puig, Josep, additional, Waite, Kristin, additional, Colen, Rivka, additional, Choi, Yoon Seong, additional, Lee, Seung-Koo, additional, Dicker, Adam P, additional, Flanders, Adam E, additional, Shi, Wenyin, additional, Griffith, Brent, additional, Poisson, Laila M, additional, Rogers, Lisa R, additional, Booth, Thomas C, additional, Jain, Rajan, additional, Chakravarti, Arnab, additional, Palmer, Joshua, additional, Mohan, Suyash, additional, Tiwari, Pallavi, additional, Aboian, Mariam, additional, Ahn, Sung Soo, additional, Davatzikos, Christos, additional, and Badve, Chaitra, additional

Published
2023
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38. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas

Author

Brat, Daniel J, Verhaak, Roel GW, Aldape, Kenneth D, Yung, WK Alfred, Salama, Sofie R, Cooper, Lee AD, Rheinbay, Esther, Miller, C Ryan, Vitucci, Mark, Morozova, Olena, Robertson, A Gordon, Noushmehr, Houtan, Laird, Peter W, Cherniack, Andrew D, Akbani, Rehan, Huse, Jason T, Ciriello, Giovanni, Poisson, Laila M, Barnholtz-Sloan, Jill S, Berger, Mitchel S, Brennan, Cameron, Colen, Rivka R, Colman, Howard, Flanders, Adam E, Giannini, Caterina, Grifford, Mia, Iavarone, Antonio, Jain, Rajan, Joseph, Isaac, Kim, Jaegil, Kasaian, Katayoon, Mikkelsen, Tom, Murray, Bradley A, O'Neill, Brian Patrick, Pachter, Lior, Parsons, Donald W, Sougnez, Carrie, Sulman, Erik P, Vandenberg, Scott R, Van Meir, Erwin G, von Deimling, Andreas, Zhang, Hailei, Crain, Daniel, Lau, Kevin, Mallery, David, Morris, Scott, Paulauskis, Joseph, Penny, Robert, Shelton, Troy, Sherman, Mark, Yena, Peggy, Black, Aaron, Bowen, Jay, Dicostanzo, Katie, Gastier-Foster, Julie, Leraas, Kristen M, Lichtenberg, Tara M, Pierson, Christopher R, Ramirez, Nilsa C, Taylor, Cynthia, Weaver, Stephanie, Wise, Lisa, Zmuda, Erik, Davidsen, Tanja, Demchok, John A, Eley, Greg, Ferguson, Martin L, Hutter, Carolyn M, Mills Shaw, Kenna R, Ozenberger, Bradley A, Sheth, Margi, Sofia, Heidi J, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean Claude, Ayala, Brenda, Baboud, Julien, Chudamani, Sudha, Jensen, Mark A, Liu, Jia, Pihl, Todd, Raman, Rohini, Wan, Yunhu, Wu, Ye, Ally, Adrian, Auman, J Todd, Balasundaram, Miruna, Balu, Saianand, Baylin, Stephen B, Beroukhim, Rameen, Bootwalla, Moiz S, Bowlby, Reanne, Bristow, Christopher A, Brooks, Denise, Butterfield, Yaron, Carlsen, Rebecca, Carter, Scott, Chin, Lynda, and Chu, Andy

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Human Genome, Brain Cancer, Rare Diseases, Neurosciences, Biotechnology, Cancer Genomics, Genetics, Cancer, Brain Disorders, Adolescent, Adult, Aged, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Cluster Analysis, DNA, Neoplasm, Female, Genes, p53, Glioblastoma, Glioma, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Neoplasm Grading, Proportional Hazards Models, Sequence Analysis, DNA, Signal Transduction, Cancer Genome Atlas Research Network, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundDiffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by interobserver variability in histologic diagnosis. Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p and 19q (1p/19q codeletion) have been implicated as clinically relevant markers of lower-grade gliomas.MethodsWe performed genomewide analyses of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression, and targeted protein expression. These data were integrated and tested for correlation with clinical outcomes.ResultsUnsupervised clustering of mutations and data from RNA, DNA-copy-number, and DNA-methylation platforms uncovered concordant classification of three robust, nonoverlapping, prognostically significant subtypes of lower-grade glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class. Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorable clinical outcomes. Their gliomas harbored mutations in CIC, FUBP1, NOTCH1, and the TERT promoter. Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in TP53 (94%) and ATRX inactivation (86%). The large majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavior strikingly similar to those found in primary glioblastoma.ConclusionsThe integration of genomewide data from multiple platforms delineated three molecular classes of lower-grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class. Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a TP53 mutation. Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to glioblastoma. (Funded by the National Institutes of Health.).

Published
2015

41. The Somatic Genomic Landscape of Glioblastoma

Author

Brennan, Cameron W, Verhaak, Roel GW, McKenna, Aaron, Campos, Benito, Noushmehr, Houtan, Salama, Sofie R, Zheng, Siyuan, Chakravarty, Debyani, Sanborn, J Zachary, Berman, Samuel H, Beroukhim, Rameen, Bernard, Brady, Wu, Chang-Jiun, Genovese, Giannicola, Shmulevich, Ilya, Barnholtz-Sloan, Jill, Zou, Lihua, Vegesna, Rahulsimham, Shukla, Sachet A, Ciriello, Giovanni, Yung, WK, Zhang, Wei, Sougnez, Carrie, Mikkelsen, Tom, Aldape, Kenneth, Bigner, Darell D, Van Meir, Erwin G, Prados, Michael, Sloan, Andrew, Black, Keith L, Eschbacher, Jennifer, Finocchiaro, Gaetano, Friedman, William, Andrews, David W, Guha, Abhijit, Iacocca, Mary, O’Neill, Brian P, Foltz, Greg, Myers, Jerome, Weisenberger, Daniel J, Penny, Robert, Kucherlapati, Raju, Perou, Charles M, Hayes, D Neil, Gibbs, Richard, Marra, Marco, Mills, Gordon B, Lander, Eric, Spellman, Paul, Wilson, Richard, Sander, Chris, Weinstein, John, Meyerson, Matthew, Gabriel, Stacey, Laird, Peter W, Haussler, David, Getz, Gad, Chin, Lynda, Network, TCGA Research, Benz, Christopher, Barrett, Wendi, Ostrom, Quinn, Wolinsky, Yingli, Bose, Bikash, Boulos, Paul T, Boulos, Madgy, Brown, Jenn, Czerinski, Christine, Eppley, Matthew, Kempista, Thelma, Kitko, Teresa, Koyfman, Yakov, Rabeno, Brenda, Rastogi, Pawan, Sugarman, Michael, Swanson, Patricia, Yalamanchii, Kennedy, Otey, Ilana P, Liu, Yingchun Spring, Xiao, Yonghong, Auman, J Todd, Chen, Peng-Chieh, Hadjipanayis, Angela, Lee, Eunjung, Lee, Semin, Park, Peter J, Seidman, Jonathan, Yang, Lixing, Kalkanis, Steven, Poisson, Laila M, Raghunathan, Aditya, Scarpace, Lisa, Bressler, Ryan, and Eakin, Andrea

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Genetics, Brain Disorders, Cancer, Biotechnology, Cancer Genomics, Neurosciences, Precision Medicine, Human Genome, Brain Cancer, Orphan Drug, Rare Diseases, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, 5.1 Pharmaceuticals, 4.2 Evaluation of markers and technologies, Brain Neoplasms, Female, Gene Expression Profiling, Gene Regulatory Networks, Glioblastoma, Humans, Male, Mutation, Proteome, Signal Transduction, TCGA Research Network, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

Published
2013

45. Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma

Author

deCarvalho, Ana C., Kim, Hoon, Poisson, Laila M., Winn, Mary E., Mueller, Claudius, Cherba, David, Koeman, Julie, Seth, Sahil, Protopopov, Alexei, Felicella, Michelle, Zheng, Siyuan, Multani, Asha, Jiang, Yongying, Zhang, Jianhua, Nam, Do-Hyun, Petricoin, Emanuel F., Chin, Lynda, Mikkelsen, Tom, and Verhaak, Roel G. W.

Published
2018
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46. Table S4 from T2–FLAIR Mismatch, an Imaging Biomarker for IDH and 1p/19q Status in Lower-grade Gliomas: A TCGA/TCIA Project

Author

Patel, Sohil H., primary, Poisson, Laila M., primary, Brat, Daniel J., primary, Zhou, Yueren, primary, Cooper, Lee, primary, Snuderl, Matija, primary, Thomas, Cheddhi, primary, Franceschi, Ana M., primary, Griffith, Brent, primary, Flanders, Adam E., primary, Golfinos, John G., primary, Chi, Andrew S., primary, and Jain, Rajan, primary

Published
2023
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47. Figure S1 from T2–FLAIR Mismatch, an Imaging Biomarker for IDH and 1p/19q Status in Lower-grade Gliomas: A TCGA/TCIA Project

Author

Patel, Sohil H., primary, Poisson, Laila M., primary, Brat, Daniel J., primary, Zhou, Yueren, primary, Cooper, Lee, primary, Snuderl, Matija, primary, Thomas, Cheddhi, primary, Franceschi, Ana M., primary, Griffith, Brent, primary, Flanders, Adam E., primary, Golfinos, John G., primary, Chi, Andrew S., primary, and Jain, Rajan, primary

Published
2023
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48. Intermittent Fasting induced ketogenesis inhibits mouse epithelial ovarian tumors by promoting anti-tumor T cell response.

Author

Udumula, Mary Priyanka, primary, Singh, Harshit, additional, Faraz, Rashid, additional, Poisson, Laila, additional, Tiwari, Nivedita, additional, Dimitrova, Irina, additional, Hijaz, Miriana, additional, Gogoi, Radhika, additional, Swenor, Margaret, additional, Munkarah, Adnan, additional, Giri, Shailendra, additional, and Rattan, Ramandeep, additional

Published
2023
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