Glioma progression is shaped by genetic evolution and microenvironment interactions

Glioma progression is shaped by genetic evolution and microenvironment interactions. Varn, F. S, Johnson, K. C, Martinek, J., Huse, J. T, Nasrallah, M. P, Wesseling, P., Cooper, L. A D, Malta, T. M, Wade, T. E, Sabedot, T. S, Brat, D., Gould, P. V, Wöehrer, A., Aldape, K., Ismail, A., Sivajothi, S. K, Barthel, F. P, Kim, H., Kocakavuk, E., Ahmed, N., White, K., Datta, I., Moon, H., Pollock, S., Goldfarb, C., Lee, G., Garofano, L., Anderson, K. J, Nehar-Belaid, D., Barnholtz-Sloan, J. S, Bakas, S., Byrne, A. T, D'Angelo, F., Gan, H. K, Khasraw, M., Migliozzi, S., Ryan Ormond, D, Paek, S. H., Van Meir, E. G, Walenkamp, A. M E, Watts, C., Weiss, T., Weller, M., Palucka, K., Stead, L. F, Poisson, L. M, Noushmehr, H., Iavarone, A., Verhaak, R. G W, Alfaro, K. D, Amin, S. B, Ashley, D. M, Bock, C., Brodbelt, A., Bulsara, K. R, Castro, A. V., Connelly, J. M, Costello, J. F, de Groot, J. F, Finocchiaro, G., French, P. J, Golebiewska, A., Hau, A. C, Hong, C., Horbinski, C., Kannan, K. S, Kouwenhoven, M. C M, Lasorella, A., LaViolette, P. S, Ligon, K. L, Lowman, A. K, Mehta, S., Miletic, H., Molinaro, A. M, Ng, H. K., Niclou, S. P, Niers, J. M, Phillips, J. J, Rabadan, R., Rao, G., Reifenberger, G., Sanai, N., Short, S. C, Smitt, P. S., Sloan, A. E, Smits, M., Snyder, J. M, Suzuki, H., Tabatabai, G., Tanner, G., Tomaszewski, W. H, Wells, M., Westerman, B. A, Wheeler, H., Xie, J., Alfred Yung, W K, Zadeh, G., Zhao, J., & Verhaak, R. G W Cell, Elsevier, 31 May, 2022.

Paper doi abstract bibtex

SummaryThe 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.

@ARTICLE{Varn2022-bt,
  title     = "{Glioma progression is shaped by genetic evolution and
               microenvironment interactions}",
  author    = "Varn, Frederick S and Johnson, Kevin C and Martinek, Jan and
               Huse, Jason T and Nasrallah, Maclean P and Wesseling, Pieter and
               Cooper, Lee A D and Malta, Tathiane M and Wade, Taylor E and
               Sabedot, Thais S and Brat, Daniel and Gould, Peter V and
               W{\"{o}}ehrer, Adelheid and Aldape, Kenneth and Ismail, Azzam and
               Sivajothi, Santhosh K and Barthel, Floris P and Kim, Hoon and
               Kocakavuk, Emre and Ahmed, Nazia and White, Kieron and Datta,
               Indrani and Moon, Hyo-Eun and Pollock, Steven and Goldfarb,
               Christine and Lee, Ga-Hyun and Garofano, Luciano and Anderson,
               Kevin J and Nehar-Belaid, Djamel and Barnholtz-Sloan, Jill S and
               Bakas, Spyridon and Byrne, Annette T and D'Angelo, Fulvio and
               Gan, Hui K and Khasraw, Mustafa and Migliozzi, Simona and Ryan
               Ormond, D and Paek, Sun Ha and Van Meir, Erwin G and Walenkamp,
               Annemiek M E and Watts, Colin and Weiss, Tobias and Weller,
               Michael and Palucka, Karolina and Stead, Lucy F and Poisson,
               Laila M and Noushmehr, Houtan and Iavarone, Antonio and Verhaak,
               Roel G W and Alfaro, Kristin D and Amin, Samirkumar B and Ashley,
               David M and Bock, Christoph and Brodbelt, Andrew and Bulsara,
               Ketan R and Castro, Ana Valeria and Connelly, Jennifer M and
               Costello, Joseph F and de Groot, John F and Finocchiaro, Gaetano
               and French, Pim J and Golebiewska, Anna and Hau, Ann C and Hong,
               Chibo and Horbinski, Craig and Kannan, Kasthuri S and
               Kouwenhoven, Mathilde C M and Lasorella, Anna and LaViolette,
               Peter S and Ligon, Keith L and Lowman, Allison K and Mehta,
               Shwetal and Miletic, Hrvoje and Molinaro, Annette M and Ng, Ho
               Keung and Niclou, Simone P and Niers, Johanna M and Phillips,
               Joanna J and Rabadan, Raul and Rao, Ganesh and Reifenberger,
               Guido and Sanai, Nader and Short, Susan C and Smitt, Peter
               Sillevis and Sloan, Andrew E and Smits, Marion and Snyder, James
               M and Suzuki, Hiromichi and Tabatabai, Ghazaleh and Tanner,
               Georgette and Tomaszewski, William H and Wells, Michael and
               Westerman, Bart A and Wheeler, Helen and Xie, Jichun and Alfred
               Yung, W K and Zadeh, Gelareh and Zhao, Junfei and Verhaak, Roel G
               W",
  journal   = "Cell",
  publisher = "Elsevier",
  volume    =  0,
  number    =  0,
  abstract  = "SummaryThe 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.",
  month     =  "31~" # may,
  year      =  2022,
  url       = "http://www.cell.com/article/S0092867422005360/abstract",
  file      = "all/V/Varn-2022__Glioma_progression_is_shaped_by_genetic_evolution_microenvironment_interactions__cell-verha.pdf",
  keywords  = "glioma; glioblastoma; genomics; treatment resistance;
               microenvironment; hypermutation; neurons; macrophages;
               single-cell; spatial
               imaging;glass;heterogeneity;evolution;tmen;thread;mynotes;lab\_website",
  doi       = "10.1016/j.cell.2022.04.038",
  issn      = "0092-8674,1097-4172",
  language  = "en",
  authorclass = {coauthor},
  contribution = {interpretation, discussion},
  affiliation = {JAX}
}

Downloads: 0