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    Cell. 2022 May 24. pii: S0092-8674(22)00536-0. doi: 10.1016/j.cell.2022.04.038
    Glioma progression is shaped by genetic evolution and microenvironment interactions.
    Varn FS1,  Johnson KC2,  Martinek J3,  Huse JT4,  Nasrallah MP5,  Wesseling P6,  Cooper LAD7,  Malta TM8,  Wade TE9,  Sabedot TS10,  Brat D11,  Gould PV12,  Wöehrer A13,  Aldape K14,  Ismail A15,  Sivajothi SK16,  Barthel FP17,  Kim H18,  Kocakavuk E19,  Ahmed N20,  White K21,  Datta I22,  Moon HE23,  Pollock S24,  Goldfarb C25,  Lee GH26,  Garofano L27,  Anderson KJ28,  Nehar-Belaid D29,  Barnholtz-Sloan JS30,  Bakas S31,  Byrne AT32,  D'Angelo F33,  Gan HK34,  Khasraw M35,  Migliozzi S36,  Ormond DR37,  Paek SH38,  Van Meir EG39,  Walenkamp AME40,  Watts C41,  Weiss T42,  Weller M43,  Palucka K44,  Stead LF45,  Poisson LM46,  Noushmehr H47,  Iavarone A48,  Verhaak RGW49
    Collaborators
    Varn FS Johnson KC Martinek J Huse JT Nasrallah MP Wesseling P Cooper LAD Malta TM Wade TE Sabedot TS Brat D Gould PV Wöehrer A Aldape K Ismail A Sivajothi SK Barthel FP Kim H Kocakavuk E Ahmed N White K Datta I Moon HE Pollock S Goldfarb C Lee GH Garofano L Anderson KJ Nehar-Belaid D Barnholtz-Sloan JS Bakas S Byrne AT D'Angelo F Gan HK Khasraw M Migliozzi S Ryan Ormond D Ha Paek S Van Meir EG Walenkamp AME Watts C Weiss T Weller M Alfaro KD Amin SB Ashley DM Bock C Brodbelt A Bulsara KR Castro AV Connelly JM Costello JF de Groot JF Finocchiaro G French PJ Golebiewska A Hau AC Hong C Horbinski C Kannan KS Kouwenhoven MC Lasorella A LaViolette PS Ligon KL Lowman AK Mehta S Miletic H Molinaro AM Ng HK Niclou SP Niers JM Phillips JJ Rabadan R Rao G Reifenberger G Sanai N Short SC Sillevis Smitt P Sloan AE Smits M Snyder JM Suzuki H Tabatabai G Tanner G Tomaszewski WH Wells M Westerman BA Wheeler H Xie J Alfred Yung WK Zadeh G Zhao J Palucka K Stead LF Poisson LM Noushmehr H Iavarone A Verhaak RG
    Author information
    1The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    2The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    3The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    4Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
    5Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
    6Amsterdam University Medical Centers/VUmc, Amsterdam, the Netherlands; Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
    7Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
    8School of Pharmaceutical Sciences of Ribeirao Preto, University of São Paulo, Brazil, Ribeirao Preto, São Paulo, Brazil.
    9The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    10Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA.
    11Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
    12service d'anatomopathologie, Hôpital de l'Enfant-Jésus du Centre hospitalier universitaire de Québec, Université Laval, Quebec City, QC, Canada.
    13Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, Vienna, Austria.
    14National Cancer Institute, Bethesda, MD, USA.
    15Department of Cellular and Molecular Pathology, Leeds Teaching Hospital NHS Trust, St James's University Hospital, Leeds, UK.
    16The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    17The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Cancer and Cell Biology Division, the Translational Genomics Research Institute, Phoenix, AZ, USA.
    18The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Department of Biopharmaceutical Convergence, Department of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeong gi-do, South Korea.
    19The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany.
    20University of Leeds, Leeds, UK.
    21Precision Cancer Medicine Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland.
    22Department of Public Health Sciences, Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA.
    23Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.
    24University of Leeds, Leeds, UK.
    25The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    26The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    27Institute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA.
    28The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    29The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    30Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, USA; Center for Biomedical Informatics and Information Technology & Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
    31Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
    32Precision Cancer Medicine Group, Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin, Ireland.
    33Institute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA.
    34Olivia Newton-John Cancer Research Institute, Austin Health, Melbourne, Australia.
    35Preston Robert Tisch Brain Tumor Center at Duke, Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
    36Institute for Cancer Genetics, Columbia University Medical Center, New York, NY, USA.
    37Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, USA.
    38Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.
    39Department of Neurosurgery, School of Medicine and O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA.
    40Department of Medical Oncology, University Medical Center Groningen, Groningen, the Netherlands.
    41Academic Department of Neurosurgery, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
    42Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zürich, Switzerland.
    43Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zürich, Switzerland.
    44The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
    45University of Leeds, Leeds, UK.
    46Department of Public Health Sciences, Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA.
    47Hermelin Brain Tumor Center, Henry Ford Health System, Detroit, MI, USA.
    48Institute for Cancer Genetics, Columbia University Medical Center, New York, NY, 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; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA.
    49The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; Department of Neurosurgery, Amsterdam University Medical Centers/VUmc, Amsterdam, the Netherlands. Electronic address: roel.verhaak@jax.org.
    Abstract

    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.


    Copyright © 2022 Elsevier Inc. All rights reserved.

    KEYWORDS: genomics, glioblastoma, glioma, hypermutation, macrophages, microenvironment, neurons, single-cell, spatial imaging, treatment resistance

    Publikations ID: 35649412
    Quelle: öffnen
     
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