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Video

Molecular pathology & classification

Session: Abstract Concurrent Session: Molecular Pathology - Classification

PATH-23 - Clinicopathologic analysis of novel methylation clusters of IDH-wildtype diffuse gliomas

Sunday, November 19, 2023
9:20 AM – 9:30 AM PT
Location: Room 118-120
Non-CME

    Author(s)

  • Omkar Singh

    Laboratory of Pathology, National Cancer Institute, NIH
    Bethesda, Maryland, United States

  • Kenneth D. Aldape

    Laboratory of Pathology, National Cancer Institute, NIH
    Bethesda, Maryland, United States

  • ZA

    Zied Abdullaev

    Laboratory of Pathology, National Cancer Institute, NIH
    Bethesda, Maryland, United States

  • RT

    Rust Turakulov

    Laboratory of Pathology, National Cancer Institute, NIH
    Bethesda, Maryland, United States

  • FA

    Felipe Andreiuolo

    Instituto Estadual do Cerebro Paulo Niemeyer
    Rio de Janeiro, Rio de Janeiro, Brazil

  • FD

    Felipe D'Almeida Costa

    AC Camargo Cancer Center
    Sao Paulo, Brazil

  • Sandra Camelo-Piragua

    University of Michigan, Ann Arbor
    Ann Arbor, Michigan, United States

  • PP

    Peter Pytel

    University of Chicago
    Chicago, Illinois, United States

  • Daniel Zhang

    University of Pennsylvania
    Philadelphia, Pennsylvania, United States

  • EB

    Ewa Borys

    Loyola University Medical Center
    Maywood, Illinois, United States

  • SN

    Stephen Nix

    UAMS Medical Center
    Little Rock, United States

  • IF

    Igor Fernandes

    Laboratorio Bacchi
    Sao Paulo, Brazil

  • ES

    Emily Sloan

    MedStar Georgetown University Hospital
    Washington DC, District of Columbia, United States

  • KP

    Kester A. Phillips

    Swedish Medical Center
    Seattle, United States

  • LN

    Luciano Neder Serafini

    Faculdade de Medicina de Ribeirão Preto
    Ribeirão Preto, Brazil

  • Jorge A. Trejo-Lopez

    Mayo Clinic
    Rochester, Minnesota, United States

  • JM

    Joe Mendez

    Huntsman Cancer Institute at the University of Utah
    Salt Lake City, Utah, United States

  • Charles G. Eberhart

    Johns Hopkins University
    Baltimore, Maryland, United States

  • MS

    Matthew Smith-Cohn

    Swedish Institute
    Seattle, Washington, United States

  • SN

    Stewart Neill

    Department of Pathology and Laboratory Medicine, School of Medicine, Emory University
    Atlanta, Georgia, United States

  • BC

    Brock C. Christensen

    Geisel School of Medicine at Dartmouth
    Lebanon, New Hampshire, United States

  • RM

    Robert Macaulay

    Moffitt Cancer Center
    Tampa, Florida, United States

  • Howard Colman

    Huntsman Cancer Institute, University of Utah
    Salt Lake City, Utah, United States

  • AN

    Aivi Nguyen

    Mayo Clinic
    Rochester, United States

  • Caterina Giannini

    Mayo Clinic
    Rochester, Minnesota, United States

  • RL

    Rong Li

    Children's of Alabama
    Birmingham, United States

  • JM

    James Mandell

    University of Virginia
    Charlottesville, United States

  • TK

    Tobias Kessler

    Dept. of Neurology, Heidelberg University Hospital, Heidelberg University,
    Heidelberg, Baden-Wurttemberg, Germany

  • Wolfgang Wick

    Universitatsklinikum Heidelberg
    Heidelberg, Baden-Wurttemberg, Germany

  • CJ

    Chris Jones

    Division of Molecular Pathology, Institute of Cancer Research
    London, United Kingdom

  • MC

    Matthew Clarke

    The Institute of Cancer Research
    London, United Kingdom

  • AM

    Alan MacKay

    The Institute of Cancer Research
    Sutton, England, United Kingdom

  • JH

    Jeffrey Helgager

    University of Wisconsin School of Medicine and Public Health
    Madison, Wisconsin, United States

  • HL

    Han Lee

    University of California, Davis
    Sacramento, United States

  • Giselle Lopez

    Duke University
    Durham, North Carolina, United States

  • Arie Perry

    University of California, San Francisco
    San Francisco, California, United States

  • SA

    Saman Ahmadian

    Ohio State University Medical Center
    Columbus, United States

  • MH

    Mohammad Haeri

    University of Kansas Medical Center
    Kansas City, United States

  • SW

    Shih-Hsiu Wang

    Duke University School of Medicine
    Durham, United States

  • SD

    Sonika Dahiya

    Department of Pathology and Immunology, Washington University
    Saint Louis, Missouri, United States

  • AS

    Andrea Souza

    D’Or Institute Research & Education
    Rio de Janeiro, Brazil

  • JV

    Joao Vitor Antunes Marques Gregorio

    D’Or Institute Research & Education
    Rio de Janeiro, United States

  • HS

    Hugo Sterman

    D’Or Institute Research & Education
    Rio de Janeiro, United States

    • Oral Abstract Presenter(s)

  • MacLean P. Nasrallah

    University of Pennsylvania, USA
    Philadelphia, Pennsylvania, United States

    • Author(s)

  • Orwa Aboud

    University of California Davis
    Sacramento, California, United States

Methylation profiling of brain tumors has revealed novel clusters whose biological and clinical significance is unknown. These include three entities termed by the 12.5 version of the Heidelberg methylation classifier as adult-type diffuse high grade glioma, IDH-wildtype, subtype B (HGG_B), subtype E (HGG_E), and subtype F (HGG_F). We have identified 75 cases belonging to these groups: HGG_B (25 cases, 32% female), HGG_E (40 cases, 42% female), and HGG_F (18 cases, 33% female). Although originally characterized as “adult-type,” we find that 70% of HGG_E cases are pediatric, with a median age at diagnosis of 11 years. HGG_B cases are predominantly seen in young adults, and HGG_F in older adults. The histology varies among methylation classes, with HGG_B cases demonstrating high-grade, predominantly astrocytic, morphology, while HGG_E cases demonstrate high-grade glial histology with distinct nuclear features, and HGG_F cases show highly infiltrative but lower grade glial morphology. Patient outcome data obtained to date shows a collective median survival exceeding 5 years, suggesting re-consideration of the proposed grading for these tumors. MGMT promoter methylation differs across the HGG_B (0%), HGG_E (12%), and HGG_F (0%) subtypes. Mutational analyses show enrichment of TERT promoter mutations in the HGG_F group, while HGG_E samples are enriched for tumors with POLE mutations and elevated tumor mutation burden. HGG_E tumors show epigenetic similarity to pediatric high-grade diffuse gliomas (pedHGG_RTK1A); we therefore propose that HGG_E be considered a pediatric-type HGG. HGG_B tumors show demographic and genomic similarities to high-grade astrocytomas with piloid features, including a subset of cases with CDKN2A/2B loss and ATRX mutation. HGG_F separate into two groups dictated by brain location, and despite the presence of TERT promoter mutations, appear distinct from GBMs. Overall, our work represents an initial effort to understand the morphologic, genomic and clinical characteristics of these previously uncharacterized subtypes of gliomas.