Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/22179
Title: Longitudinal molecular trajectories of diffuse glioma in adults.
Austin Authors: 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
Affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Austin Health, Heidelberg, Victoria, Australia
Department of Pathology, Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
DKFZ Division of Translational Neurooncology at the West German Cancer Center, German Cancer Consortium Partner Site, University Hospital Essen, Essen, Germany
Department of Neurosurgery, University Hospital Essen, Essen, Germany
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC, USA
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
Broad Institute, Cambridge, MA, USA
Department of Population and Quantitative Health Sciences, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Broad Institute, Cambridge, MA, USA
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Division of Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA
Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Department of Neurosurgery, University of Liverpool & Walton Centre NHS Trust, Liverpool, UK
Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
Division of Neurosurgery, The University of Connecticut Health Center, Farmington, CT, USA
Department of Cellular and Molecular Pathology, Leeds Teaching Hospital NHS Trust, St James's University Hospital, Leeds, UK
Department of Radiation Oncology, The Ohio State Comprehensive Cancer Center-Arthur G. James Cancer Hospital, Columbus, OH, USA
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, USA
Yale University School of Public Health, New Haven, CT, USA
Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA
Department of Pathology & Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, USA
Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA
Fondazione IRCCS Istituto Neurologico Besta, Milano, Italy
Division of Molecular Genetics, Heidelberg Center for Personalized Oncology, German Cancer Research Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neurology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands
La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia
Neuro-Oncology Branch, National Institutes of Health, Bethesda, MD, USA
Anatomic Pathology Service, Hôpital de l'Enfant-Jésus, CHU de Québec-Université Laval, Quebec, Quebec, Canada
Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA
Department of Neurology, Columbia University Medical Center, New York, NY, USA
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA
Institute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA
Department of Cellular and Molecular Pathology, Leeds Teaching Hospital NHS Trust, St James's University Hospital, Leeds, UK
Department of Neurosurgery, University of Liverpool & Walton Centre NHS Trust, Liverpool, UK
Cooperative Trials Group for Neuro-Oncology (COGNO) NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Department of Neurology, Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Division of Molecular Genetics, Heidelberg Center for Personalized Oncology, German Cancer Research Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany
Broad Institute, Cambridge, MA, USA
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA
Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA
Department of Neurosurgery, Henry Ford Health System, Henry Ford Cancer Institute, Detroit, MI, USA
Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA
Cure Brain Cancer Biomarkers and Translational Research Group, Prince of Wales Clinical School, University of New South Wales, Sydney, New South Wales, Australia
Department of Neurosurgery, University of California San Francisco, San Francisco, CA, USA
Department of Neurosurgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea
Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, South Korea
Division of Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Department of Oncology, Luxembourg Institute of Health, Luxembourg, Luxembourg
Department of Neurology, Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Department of Neurosurgery, Henry Ford Health System, Henry Ford Cancer Institute, Detroit, MI, USA
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, USA
Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea
Department of Public Health Sciences, Henry Ford Health System, Henry Ford Cancer Institute, Detroit, MI, USA
Department of Biomedical Informatics, Columbia University Medical Center, New York, NY, USA
Department of Systems Biology, Columbia University, New York, NY, USA
Division of Molecular Genetics, Heidelberg Center for Personalized Oncology, German Cancer Research Consortium, German Cancer Research Center (DKFZ), Heidelberg, Germany
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Institute of Neuropathology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, South Korea
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Division of Neuro-Oncology, Massachusetts General Hospital, Boston, MA, USA
Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
Department of Neurology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Neurological Surgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA
Department of Neurosurgery, Case Western Reserve University, Cleveland, OH, USA
Seidman Cancer Center and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA
Department of Radiology & Nuclear Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands
The Hospital for Sick Children, Toronto, ON, Canada
Interdiscplinary Division of Neuro-Oncology, Hertie Institute for Clinical Brain Research, DKTK Partner Site Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany
Department of Neurosurgery, School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA, USA
Institute of Cancer Genome Sciences, Department of Neurosurgery, University of Birmingham, Birmingham, UK
Department of Neurology, University Hospital Zurich, Zurich, Switzerland
Department of Pathology, Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Neurosurgery, Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
Department of Neurosurgery, Medical University of Vienna, Vienna, Austria
Institute of Neurology, Medical University of Vienna, Vienna, Austria
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Division of Neurosurgery, Department of Surgery, University Health Network, Toronto, Ontario, Canada
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Issue Date: 2019
metadata.dc.date: 2019-11-20
Publication information: 2019; 576(7785): 112-120
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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22179
DOI: 10.1038/s41586-019-1775-1
PubMed URL: 31748746
Type: Journal Article
Appears in Collections:Journal articles

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