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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 Department of Pathology, Brain Tumor Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia Austin Health, Heidelberg, Victoria, Australia 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 | 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: | https://ahro.austin.org.au/austinjspui/handle/1/22179 | DOI: | 10.1038/s41586-019-1775-1 | Journal: | Nature | PubMed URL: | 31748746 | Type: | Journal Article |
| Appears in Collections: | Journal articles |
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