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10. Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas.

Author

Wang, Justin Z, Patil, Vikas, Liu, Jeff, Dogan, Helin, Tabatabai, Ghazaleh, Yefet, Leeor S, Behling, Felix, Hoffman, Elgin, Bunda, Severa, Yakubov, Rebecca, Kaloti, Ramneet, Brandner, Sebastian, Gao, Andrew, Cohen-Gadol, Aaron, Barnholtz-Sloan, Jill, Skardelly, Marco, Tatagiba, Marcos, Raleigh, David R, Sahm, Felix, Boutros, Paul C, Aldape, Kenneth, International Consortium on Meningiomas (ICOM), Nassiri, Farshad, and Zadeh, Gelareh

Subjects
International Consortium on Meningiomas, Humans, Meningioma, Meningeal Neoplasms, Sequence Deletion, Homozygote, Genes, p16, Cyclin-Dependent Kinase Inhibitor p16, DNA Copy Number Variations, Transcriptome, CDK inhibitor, CDKN2A, Copy number alterations, Meningiomas, Multiomic, Retinoblastoma, Cancer, Human Genome, Genetics, Brain Disorders, Biotechnology, Clinical Sciences, Neurosciences, Neurology & Neurosurgery
Abstract

Homozygous deletion of CDKN2A/B was recently incorporated into the World Health Organization classification for grade 3 meningiomas. While this marker is overall rare in meningiomas, its relationship to other CDKN2A alterations on a transcriptomic, epigenomic, and copy number level has not yet been determined. We therefore utilized multidimensional molecular data of 1577 meningioma samples from 6 independent cohorts enriched for clinically aggressive meningiomas to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach. Homozygous CDKN2A/B deletions were identified in only 7.1% of cases but were associated with significantly poorer outcomes compared to tumors without these deletions. Heterozygous CDKN2A/B deletions were identified in 2.6% of cases and had similarly poor outcomes as those with homozygous deletions. Among tumors with intact CDKN2A/B (without a homozygous or heterozygous deletion), we found a distinct difference in outcome based on mRNA expression of CDKN2A, with meningiomas that had elevated mRNA expression (CDKN2Ahigh) having a significantly shorter time to recurrence. The expression of CDKN2A was independently prognostic after accounting for copy number loss and consistently increased with WHO grade and more aggressive molecular and methylation groups irrespective of cohort. Despite the discordant and mutually exclusive status of the CDKN2A gene in these groups, both CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycle pathways but at different checkpoints. High mRNA expression of CDKN2A was also associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. p16 immunohistochemistry could not reliably differentiate between meningiomas with and without CDKN2A deletions but appeared to correlate better with mRNA expression. These findings support the role of CDKN2A mRNA expression as a biomarker of clinically aggressive meningiomas with potential therapeutic implications.

Published
2023

11. EPS as an Inclusion Material: An Instrumented Field Study on Retaining Wall

Author

Bishnoi, Dinesh, Patil, Vikas, Dasaka, S. M., di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Cui, Zhen-Dong, Series Editor, Hazarika, Hemanta, editor, Haigh, Stuart Kenneth, editor, Chaudhary, Babloo, editor, Murai, Masanori, editor, and Manandhar, Suman, editor

Published
2024
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12. The Development of the Semiconductor Supply Chain in India: Challenges and Opportunities

Author

Sonawane, Manik Sadashiv, Pawar, Sanjay Shamrao, Patil, Jayamala Kumar, Patil, Vikas Dattatray, Kacprzyk, Janusz, Series Editor, Gomide, Fernando, Advisory Editor, Kaynak, Okyay, Advisory Editor, Liu, Derong, Advisory Editor, Pedrycz, Witold, Advisory Editor, Polycarpou, Marios M., Advisory Editor, Rudas, Imre J., Advisory Editor, Wang, Jun, Advisory Editor, Kaiser, M. Shamim, editor, Xie, Juanying, editor, and Rathore, Vijay Singh, editor

Published
2024
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15. Oncolytic DNX-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1/2 trial.

Author

Nassiri, Farshad, Patil, Vikas, Yefet, Leeor, Singh, Olivia, Liu, Jeff, Dang, Rachel, Yamaguchi, Takafumi, Daras, Mariza, Cloughesy, Timothy, Colman, Howard, Kumthekar, Priya, Chen, Clark, Aiken, Robert, Groves, Morris, Ong, Shirley, Ramakrishna, Rohan, Vogelbaum, Michael, Khagi, Simon, Kaley, Thomas, Melear, Jason, Peereboom, David, Rodriguez, Analiz, Yankelevich, Maxim, Nair, Suresh, Puduvalli, Vinay, Aldape, Kenneth, Gao, Andrew, López-Janeiro, Álvaro, de Andrea, Carlos, Alonso, Marta, Boutros, Paul, Robbins, Joan, Mason, Warren, Sonabend, Adam, Stupp, Roger, Fueyo, Juan, Gomez-Manzano, Candelaria, Lang, Frederick, and Zadeh, Gelareh

Subjects
Humans, Glioblastoma, Neoplasm Recurrence, Local, Antibodies, Monoclonal, Humanized, Oncolytic Virotherapy, Oncolytic Viruses, Antineoplastic Combined Chemotherapy Protocols
Abstract

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab in recurrent glioblastoma, first in a dose-escalation and then in a dose-expansion phase, in 49 patients. The primary endpoints were overall safety and objective response rate. The primary safety endpoint was met, whereas the primary efficacy endpoint was not met. There were no dose-limiting toxicities, and full dose combined treatment was well tolerated. The objective response rate was 10.4% (90% confidence interval (CI) 4.2-20.7%), which was not statistically greater than the prespecified control rate of 5%. The secondary endpoint of overall survival at 12 months was 52.7% (95% CI 40.1-69.2%), which was statistically greater than the prespecified control rate of 20%. Median overall survival was 12.5 months (10.7-13.5 months). Objective responses led to longer survival (hazard ratio 0.20, 95% CI 0.05-0.87). A total of 56.2% (95% CI 41.1-70.5%) of patients had a clinical benefit defined as stable disease or better. Three patients completed treatment with durable responses and remain alive at 45, 48 and 60 months. Exploratory mutational, gene-expression and immunophenotypic analyses revealed that the balance between immune cell infiltration and expression of checkpoint inhibitors may potentially inform on response to treatment and mechanisms of resistance. Overall, the combination of intratumoral DNX-2401 followed by pembrolizumab was safe with notable survival benefit in select patients (ClinicalTrials.gov registration: NCT02798406).

Published
2023

17. Early rhombic lip Protogenin+ve stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma

Author

Visvanathan, Abhirami, Saulnier, Olivier, Chen, Chuan, Haldipur, Parthiv, Orisme, Wilda, Delaidelli, Alberto, Shin, Seungmin, Millman, Jake, Bryant, Andrew, Abeysundara, Namal, Wu, Xujia, Hendrikse, Liam D., Patil, Vikas, Bashardanesh, Zahedeh, Golser, Joseph, Livingston, Bryn G., Nakashima, Takuma, Funakoshi, Yusuke, Ong, Winnie, Rasnitsyn, Alexandra, Aldinger, Kimberly A., Richman, Cory M., Van Ommeren, Randy, Lee, John J.Y., Ly, Michelle, Vladoiu, Maria C., Kharas, Kaitlin, Balin, Polina, Erickson, Anders W., Fong, Vernon, Zhang, Jiao, Suárez, Raúl A., Wang, Hao, Huang, Ning, Pallota, Jonelle G., Douglas, Tajana, Haapasalo, Joonas, Razavi, Ferechte, Silvestri, Evelina, Sirbu, Olga, Worme, Samantha, Kameda-Smith, Michelle M., Wu, Xiaochong, Daniels, Craig, MichaelRaj, Antony K., Bhaduri, Aparna, Schramek, Daniel, Suzuki, Hiromichi, Garzia, Livia, Ahmed, Nabil, Kleinman, Claudia L., Stein, Lincoln D., Dirks, Peter, Dunham, Christopher, Jabado, Nada, Rich, Jeremy N., Li, Wei, Sorensen, Poul H., Wechsler-Reya, Robert J., Weiss, William A., Millen, Kathleen J., Ellison, David W., Dimitrov, Dimiter S., and Taylor, Michael D.

Published
2024
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22. Multiplatform molecular profiling uncovers two subgroups of malignant peripheral nerve sheath tumors with distinct therapeutic vulnerabilities

Author

Suppiah, Suganth, Mansouri, Sheila, Mamatjan, Yasin, Liu, Jeffrey C., Bhunia, Minu M., Patil, Vikas, Rath, Prisni, Mehani, Bharati, Heir, Pardeep, Bunda, Severa, Velez-Reyes, German L., Singh, Olivia, Ijad, Nazanin, Pirouzmand, Neda, Dalcourt, Tatyana, Meng, Ying, Karimi, Shirin, Wei, Qingxia, Nassiri, Farshad, Pugh, Trevor J., Bader, Gary D., Aldape, Kenneth D., Largaespada, David A., and Zadeh, Gelareh

Published
2023
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33. Fractionated radiotherapy for surgically resected intracranial meningiomas: A multicentre retrospective cohort study

Author

Wang, Justin Z., Nassiri, Farshad, Landry, Alexander P, Patil, Vikas, Rebchuk, Alexander, Merali, Zamir A., Gui, Chloe, Lee, Grace, Rogers, Lauren, Sinha, Jessica, Patel, Zeel, Zuccato, Jeffrey A., Voisin, Mathew R., Munoz, David, Spears, Julian, Cusimano, Michael D., Das, Sunit, Makarenko, Serge, Yip, Stephen, Gao, Andrew, Laperriere, Normand, Tsang, Derek S., and Zadeh, Gelareh

Published
2023
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37. Correction: Increased mRNA expression of CDKN2A is a transcriptomic marker of clinically aggressive meningiomas

Author

Wang, Justin Z., Patil, Vikas, Liu, Jeff, Dogan, Helin, Tabatabai, Ghazaleh, Yefet, Leeor S., Behling, Felix, Hoffman, Elgin, Bunda, Severa, Yakubov, Rebecca, Kaloti, Ramneet, Brandner, Sebastian, Gao, Andrew, Cohen-Gadol, Aaron, Barnholtz-Sloan, Jill, Skardelly, Marco, Tatagiba, Marcos, Raleigh, David R., Sahm, Felix, Boutros, Paul C., Aldape, Kenneth, Nassiri, Farshad, and Zadeh, Gelareh

Published
2023
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41. Development of a Full-Scale Retaining Wall Model to Evaluate Lateral Earth Pressure Reduction Using EPS Geofoam

Author

Patil, Vikas, Junagade, Mrunmay, Murty, Dasaka S., di Prisco, Marco, Series Editor, Chen, Sheng-Hong, Series Editor, Vayas, Ioannis, Series Editor, Kumar Shukla, Sanjay, Series Editor, Sharma, Anuj, Series Editor, Kumar, Nagesh, Series Editor, Wang, Chien Ming, Series Editor, Satyanarayana Reddy, C. N. V., editor, Krishna, A. Murali, editor, and Satyam, Neelima, editor

Published
2022
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46. A phase II trial of olaparib and durvalumab in patients with recurrent IDH-mutated gliomas.

Author

Wang, Xin, primary, Ellenbogen, Yosef, additional, Mojica, Christianne, additional, Matos, Gustavo Duarte Ramos, additional, Alsajjan, Roa, additional, Ramos, Ronald, additional, Climans, Seth Andrew, additional, Voisin, Mathew, additional, Patil, Vikas, additional, Baker, Stephanie, additional, Chan, Yin-Ling, additional, Pimentel Muniz, Thiago, additional, Gao, Andrew, additional, Wang, Ben X, additional, Zadeh, Gelareh, additional, Mason, Warren P., additional, and Chen, Eric Xueyu, additional

Published
2024
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47. Incidence of germline genetic testing in Veterans with breast cancer in the Veterans Health Administration.

Author

Halwani, Ahmad Sami, primary, Patil, Vikas, additional, Mcshinsky, Richard, additional, Morreall, Deborah, additional, Rasmussen, Kelli M, additional, Li, Chunyang, additional, Burningham, Zachary R., additional, Menendez, Carolyn S., additional, Chiba, Akiko, additional, Moss, Haley, additional, Colonna, Sarah Violet, additional, Rowe, Kerry G., additional, and Kelley, Michael J., additional

Published
2024
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48. Implementing a natural language processing pipeline to expedite clinical chart review to assess germline genetic testing in veterans with breast cancer.

Author

Patil, Vikas, primary, Mcshinsky, Richard, additional, Halwani, Ahmad Sami, additional, Morreall, Deborah, additional, Li, Chunyang, additional, Rasmussen, Kelli M, additional, Yong, Christina, additional, Burningham, Zachary R., additional, Menendez, Carolyn S., additional, Chiba, Akiko, additional, Moss, Haley, additional, Colonna, Sarah Violet, additional, Rowe, Kerry G., additional, and Kelley, Michael J., additional

Published
2024
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