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Glioma progression is shaped by genetic evolution and microenvironment interactions

2022; Cell Press; Volume: 185; Issue: 12 Linguagem: Inglês

10.1016/j.cell.2022.04.038

1097-4172

Frederick S. Varn, Kevin C. Johnson, Jan Martínek, Jason T. Huse, MacLean P. Nasrallah, Pieter Wesseling, Lee Cooper, Tathiane M. Malta, Taylor Wade, Thaís S. Sabedot, Daniel J. Brat, Peter V. Gould, Adelheid Wöehrer, Kenneth Aldape, Azzam Ismail, Santhosh Sivajothi, Floris P Barthel, Hoon Kim, Emre Kocakavuk, Nazia Ahmed, Kieron White, Indrani Datta, Hyo-Eun Moon, Steven Pollock, Christine N. Goldfarb, Ga-Hyun Lee, Luciano Garofano, Kevin Anderson, Djamel Nehar-Belaid, Jill S. Barnholtz‐Sloan, Spyridon Bakas, Annette T. Byrne, Fulvio D’Angelo, Hui Gan, Mustafa Khasraw, Simona Migliozzi, D. Ryan Ormond, Sun Ha Paek, Erwin G. Van Meir, Annemiek Walenkamp, Colin Watts, Tobias Weiß, Michael Weller, Karolina Palucka, Lucy F. Stead, Laila Poisson, Houtan Noushmehr, Antonio Iavarone, Roel G.W. Verhaak, Frederick S. Varn, Kevin C. Johnson, Jan Martínek, Jason T. Huse, MacLean P. Nasrallah, Pieter Wesseling, Lee Cooper, Tathiane M. Malta, Taylor Wade, Thaís S. Sabedot, Daniel J. Brat, Peter V. Gould, Adelheid Wöehrer, Kenneth Aldape, Azzam Ismail, Santhosh Sivajothi, Floris P Barthel, Hoon Kim, Emre Kocakavuk, Nazia Ahmed, Kieron White, Indrani Datta, Hyo-Eun Moon, Steven Pollock, Christine N. Goldfarb, Ga-Hyun Lee, Luciano Garofano, Kevin Anderson, Djamel Nehar-Belaid, Jill S. Barnholtz‐Sloan, Spyridon Bakas, Annette T. Byrne, Fulvio D’Angelo, Hui Gan, Mustafa Khasraw, Simona Migliozzi, D. Ryan Ormond, Sun Ha Paek, Erwin G. Van Meir, Annemiek Walenkamp, Colin Watts, Tobias Weiß, Michael Weller, Kristin Alfaro-Munoz, Samirkumar B. Amin, David M. Ashley, Christoph Bock, Andrew Brodbelt, Ketan R. Bulsara, Ana Valéria Castro, Jennifer Connelly, J Costello, John F. de Groot, Gaetano Finocchiaro, Pim J. French, Anna Golebiewska, Ann‐Christin Hau, Chibo Hong, Craig Horbinski, Kasthuri Kannan, Mathilde C.M. Kouwenhoven, Anna Lasorella, Peter S. LaViolette, Keith L. Ligon, Allison Lowman, Shwetal Mehta, Hrvoje Miletić, Annette M. Molinaro, Ho‐Keung Ng, Simone P. Niclou, Johanna M. Niers, Joanna J. Phillips, Raúl Rabadán, Hui Gan, Guido Reifenberger, Nader Sanai, Susan Short, Peter Sillevis Smitt, Andrew E. Sloan, Marion Smits, James M. Snyder, Hiromichi Suzuki, Ghazaleh Tabatabai, Georgette Tanner, William H. Tomaszewski, Michael Wells, Bart A. Westerman, Helen Wheeler, Jichun Xie, W.K. Alfred Yung, Gelareh Zadeh, Junfei Zhao, Karolina Palucka, Lucy F. Stead, Laila Poisson, Houtan Noushmehr, Antonio Iavarone, Roel G.W. Verhaak,

MicroRNA in disease regulation

Summary 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.