Longitudinal molecular trajectories of diffuse glioma in adults

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 C. M.; LaViolette, Peter S.; Li, Meihong; Lichter, Peter; Ligon, Keith L.; Lowman, Allison K.; Malta, Tathiane M.; Mazor, Tali; McDonald, Kerrie L.

doi:10.1038/s41586-019-1775-1

Cited by 561

The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.

Longitudinal molecular trajectories of diffuse glioma in adults

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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 C. M., 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, W. K. Alfred, Zadeh, Gelareh, Huse, Jason T., De Groot, John F., Stead, Lucy F., Verhaak, Roel G. W., The GLASS Consortium, Barthel, Floris P., Johnson, Kevin C., Varn, Frederick S., Moskalik, Anzhela D., Tanner, Georgette, Kocakavuk, Emre, Anderson, Kevin J., Aldape, Kenneth, Alfaro, Kristin D., 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., Bulsara, Ketan R., Chakrabarty, Aruna, 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., Iavarone, Antonio, Ismail, Azzam, Jenkinson, Michael D., Khasraw, Mustafa, Kim, Hoon, Kouwenhoven, Mathilde C. M., LaViolette, Peter S., Lichter, Peter, Ligon, Keith L., Lowman, Allison K., Malta, Tathiane M., McDonald, Kerrie L., Molinaro, Annette M., Nam, Do-Hyun, Ng, Ho Keung, Niclou, Simone P., Niers, Johanna M., Noushmehr, Houtan, Ormond, D. Ryan, Park, Chul-Kee, Poisson, Laila M., Rabadan, Raul, Radlwimmer, Bernhard, Rao, Ganesh, Reifenberger, Guido, Sa, Jason K., 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., Woehrer, Adelheid, Yung, W. K. Alfred, Zadeh, Gelareh, Huse, Jason T., De Groot, John F., Stead, Lucy F., Verhaak, Roel G. W.·2019·Nature

DOI 10.1038/s41586-019-1775-1

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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. The GLASS Consortium studies the evolutionary trajectories of 222 patients with a diffuse glioma to aid in our understanding of tumour progression and treatment failure

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Authors: Barthel, F. P., Johnson, K. C., Varn, F. S., Moskalik, A. D., Tanner, G., Kocakavuk, E., Anderson, K. J., Abiola, O., Aldape, K., Alfaro, K. D., Alpar, D., Amin, S. B., Ashley, D. M., Bandopadhayay, P., Barnholtz-Sloan, J. S., Beroukhim, R., Bock, C., Brastianos, P. K., Brat, D. J., Brodbelt, A. R., Bruns, A. F., Bulsara, K. R., Chakrabarty, A., Chakravarti, A., Chuang, J. H., Claus, E. B., Cochran, E. J., Connelly, J., Costello, J. F., Finocchiaro, G., Fletcher, M. N., French, P. J., Gan, H. K., Gilbert, M. R., Gould, P. V., Grimmer, M. R., Iavarone, A., Ismail, A., Jenkinson, M. D., Khasraw, M., Kim, H., Kouwenhoven, M. C. M., LaViolette, P. S., Li, M., Lichter, P., Ligon, K. L., Lowman, A. K., Malta, T. M., Mazor, T., McDonald, K. L., Molinaro, A. M., Nam, D.-H., Nayyar, N., Ng, H. K., Ngan, C. Y., Niclou, S. P., Niers, J. M., Noushmehr, H., Noorbakhsh, J., Ormond, D. R., Park, C.-K., Poisson, L. M., Rabadan, R., Radlwimmer, B., Rao, G., Reifenberger, G., Sa, J. K., Schuster, M., Shaw, B. L., Short, S. C., Smitt, P. A. S., Sloan, A. E., Smits, M., Suzuki, H., Tabatabai, G., Van Meir, E. G., Watts, C., Weller, M., Wesseling, P., Westerman, B. A., Widhalm, G., Woehrer, A., Yung, W. K. A., Zadeh, G., Huse, J. T., De Groot, J. F., Stead, L. F., Verhaak, R. G. W., The GLASS Consortium, Barthel, F. P., Johnson, K. C., Varn, F. S., Moskalik, A. D., Tanner, G., Kocakavuk, E., Anderson, K. J., Aldape, K., Alfaro, K. D., Amin, S. B., Ashley, D. M., Bandopadhayay, P., Barnholtz-Sloan, J. S., Beroukhim, R., Bock, C., Brastianos, P. K., Brat, D. J., Brodbelt, A. R., Bulsara, K. R., Chakrabarty, A., Chuang, J. H., Claus, E. B., Cochran, E. J., Connelly, J., Costello, J. F., Finocchiaro, G., Fletcher, M. N., French, P. J., Gan, H. K., Gilbert, M. R., Gould, P. V., Iavarone, A., Ismail, A., Jenkinson, M. D., Khasraw, M., Kim, H., Kouwenhoven, M. C. M., LaViolette, P. S., Lichter, P., Ligon, K. L., Lowman, A. K., Malta, T. M., McDonald, K. L., Molinaro, A. M., Nam, D.-H., Ng, H. K., Niclou, S. P., Niers, J. M., Noushmehr, H., Ormond, D. R., Park, C.-K., Poisson, L. M., Rabadan, R., Radlwimmer, B., Rao, G., Reifenberger, G., Sa, J. K., Short, S. C., Smitt, P. A. S., Sloan, A. E., Smits, M., Suzuki, H., Tabatabai, G., Van Meir, E. G., Watts, C., Weller, M., Wesseling, P., Westerman, B. A., Woehrer, A., Yung, W. K. A., Zadeh, G., Huse, J. T., De Groot, J. F., Stead, L. F., & Verhaak, R. G. W.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2019-11-20
Volume: 576
Issue: 7785
Pages: 112-120
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-019-1775-1
OpenAlex: W2980663762
Cited by: 561
References: 70
FWCI: 26.98
Type: journal article
Language: en
Open access: bronze

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The paper: Barthel, F. P., Johnson, K. C., Varn, F. S., Moskalik, A. D., Tanner, G., Kocakavuk, E., Anderson, K. J., Abiola, O., Aldape, K., Alfaro, K. D., Alpar, D., Amin, S. B., Ashley, D. M., Bandopadhayay, P., Barnholtz-Sloan, J. S., Beroukhim, R., Bock, C., Brastianos, P. K., Brat, D. J., . . . Verhaak, R. G. W. (2019). Longitudinal molecular trajectories of diffuse glioma in adults. Nature. https://doi.org/10.1038/s41586-019-1775-1

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Longitudinal molecular trajectories of diffuse glioma in adults

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