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Longitudinal molecular trajectories of diffuse glioma in adults

Author

Listed:
  • Floris P. Barthel

    (The Jackson Laboratory for Genomic Medicine
    Amsterdam UMC, Vrije Universiteit Amsterdam)

  • Kevin C. Johnson

    (The Jackson Laboratory for Genomic Medicine)

  • Frederick S. Varn

    (The Jackson Laboratory for Genomic Medicine)

  • Anzhela D. Moskalik

    (The Jackson Laboratory for Genomic Medicine)

  • Georgette Tanner

    (University of Leeds)

  • Emre Kocakavuk

    (The Jackson Laboratory for Genomic Medicine
    University Hospital Essen
    University Hospital Essen)

  • Kevin J. Anderson

    (The Jackson Laboratory for Genomic Medicine)

  • Olajide Abiola

    (The Jackson Laboratory for Genomic Medicine)

  • Kenneth Aldape

    (National Cancer Institute)

  • Kristin D. Alfaro

    (The University of Texas MD Anderson Cancer Center)

  • Donat Alpar

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    Semmelweis University)

  • Samirkumar B. Amin

    (The Jackson Laboratory for Genomic Medicine)

  • David M. Ashley

    (Duke University Medical Center)

  • Pratiti Bandopadhayay

    (Dana-Farber Cancer Institute
    Broad Institute)

  • Jill S. Barnholtz-Sloan

    (Case Western Reserve University School of Medicine)

  • Rameen Beroukhim

    (Broad Institute
    Dana-Farber Cancer Institute)

  • Christoph Bock

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
    Medical University of Vienna)

  • Priscilla K. Brastianos

    (Massachusetts General Hospital)

  • Daniel J. Brat

    (Northwestern University Feinberg School of Medicine)

  • Andrew R. Brodbelt

    (University of Liverpool & Walton Centre NHS Trust)

  • Alexander F. Bruns

    (University of Leeds)

  • Ketan R. Bulsara

    (The University of Connecticut Health Center)

  • Aruna Chakrabarty

    (St James’s University Hospital)

  • Arnab Chakravarti

    (The Ohio State Comprehensive Cancer Center–Arthur G. James Cancer Hospital)

  • Jeffrey H. Chuang

    (The Jackson Laboratory for Genomic Medicine
    UConn Health)

  • Elizabeth B. Claus

    (Yale University School of Public Health
    Brigham and Women’s Hospital)

  • Elizabeth J. Cochran

    (Medical College of Wisconsin)

  • Jennifer Connelly

    (Medical College of Wisconsin)

  • Joseph F. Costello

    (University of California San Francisco)

  • Gaetano Finocchiaro

    (Fondazione IRCCS Istituto Neurologico Besta)

  • Michael N. Fletcher

    (German Cancer Research Center (DKFZ))

  • Pim J. French

    (Erasmus MC – University Medical Center Rotterdam)

  • Hui K. Gan

    (Austin Health, Melbourne
    La Trobe University School of Cancer Medicine)

  • Mark R. Gilbert

    (National Institutes of Health)

  • Peter V. Gould

    (Hôpital de l’Enfant-Jésus, CHU de Québec-Université Laval)

  • Matthew R. Grimmer

    (University of California San Francisco)

  • Antonio Iavarone

    (Columbia University Medical Center
    Columbia University Medical Center
    Columbia University Medical Center)

  • Azzam Ismail

    (St James’s University Hospital)

  • Michael D. Jenkinson

    (University of Liverpool & Walton Centre NHS Trust)

  • Mustafa Khasraw

    (The University of Sydney)

  • Hoon Kim

    (The Jackson Laboratory for Genomic Medicine)

  • Mathilde C. M. Kouwenhoven

    (Vrije Universiteit Amsterdam)

  • Peter S. LaViolette

    (Medical College of Wisconsin)

  • Meihong Li

    (The Jackson Laboratory for Genomic Medicine)

  • Peter Lichter

    (German Cancer Research Center (DKFZ))

  • Keith L. Ligon

    (Broad Institute
    Dana-Farber Cancer Institute)

  • Allison K. Lowman

    (Medical College of Wisconsin)

  • Tathiane M. Malta

    (Henry Ford Cancer Institute)

  • Tali Mazor

    (University of California San Francisco)

  • Kerrie L. McDonald

    (University of New South Wales)

  • Annette M. Molinaro

    (University of California San Francisco)

  • Do-Hyun Nam

    (Sungkyunkwan University School of Medicine, Samsung Medical Center
    Samsung Medical Center)

  • Naema Nayyar

    (Massachusetts General Hospital)

  • Ho Keung Ng

    (The Chinese University of Hong Kong, Prince of Wales Hospital)

  • Chew Yee Ngan

    (The Jackson Laboratory for Genomic Medicine)

  • Simone P. Niclou

    (Luxembourg Institute of Health)

  • Johanna M. Niers

    (Vrije Universiteit Amsterdam)

  • Houtan Noushmehr

    (Henry Ford Cancer Institute)

  • Javad Noorbakhsh

    (The Jackson Laboratory for Genomic Medicine)

  • D. Ryan Ormond

    (University of Colorado School of Medicine)

  • Chul-Kee Park

    (Seoul National University College of Medicine, Seoul National University Hospital)

  • Laila M. Poisson

    (Henry Ford Cancer Institute)

  • Raul Rabadan

    (Columbia University Medical Center
    Columbia University)

  • Bernhard Radlwimmer

    (German Cancer Research Center (DKFZ))

  • Ganesh Rao

    (The University of Texas MD Anderson Cancer Center)

  • Guido Reifenberger

    (Heinrich Heine University Düsseldorf)

  • Jason K. Sa

    (Samsung Medical Center)

  • Michael Schuster

    (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

  • Brian L. Shaw

    (Massachusetts General Hospital)

  • Susan C. Short

    (University of Leeds)

  • Peter A. Sillevis Smitt

    (Erasmus MC – University Medical Center Rotterdam)

  • Andrew E. Sloan

    (Case Western Reserve University
    Case Western Reserve University
    Case Western Reserve University)

  • Marion Smits

    (Erasmus MC – University Medical Center Rotterdam)

  • Hiromichi Suzuki

    (The Hospital for Sick Children)

  • Ghazaleh Tabatabai

    (DKTK Partner Site Tübingen, Eberhard Karls University Tübingen)

  • Erwin G. Meir

    (School of Medicine and Winship Cancer Institute of Emory University)

  • Colin Watts

    (University of Birmingham)

  • Michael Weller

    (University Hospital Zurich)

  • Pieter Wesseling

    (Amsterdam UMC, Vrije Universiteit Amsterdam
    Princess Máxima Center for Pediatric Oncology)

  • Bart A. Westerman

    (Amsterdam UMC, Vrije Universiteit Amsterdam)

  • Georg Widhalm

    (Medical University of Vienna)

  • Adelheid Woehrer

    (Medical University of Vienna)

  • W. K. Alfred Yung

    (The University of Texas MD Anderson Cancer Center)

  • Gelareh Zadeh

    (University Health Network)

  • Jason T. Huse

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • John F. Groot

    (The University of Texas MD Anderson Cancer Center)

  • Lucy F. Stead

    (University of Leeds)

  • Roel G. W. Verhaak

    (The Jackson Laboratory for Genomic Medicine)

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.

Suggested Citation

  • Floris P. Barthel & Kevin C. Johnson & Frederick S. Varn & Anzhela D. Moskalik & Georgette Tanner & Emre Kocakavuk & Kevin J. Anderson & Olajide Abiola & Kenneth Aldape & Kristin D. Alfaro & Donat Alp, 2019. "Longitudinal molecular trajectories of diffuse glioma in adults," Nature, Nature, vol. 576(7785), pages 112-120, December.
  • Handle: RePEc:nat:nature:v:576:y:2019:i:7785:d:10.1038_s41586-019-1775-1
    DOI: 10.1038/s41586-019-1775-1
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    Cited by:

    1. Xing Cheng & Jing An & Jitong Lou & Qisheng Gu & Weimin Ding & Gaith Nabil Droby & Yilin Wang & Chenghao Wang & Yanzhe Gao & Jay Ramanlal Anand & Abigail Shelton & Andrew Benson Satterlee & Breanna Ma, 2024. "Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Carter J. Barger & Abigail K. Suwala & Katarzyna M. Soczek & Albert S. Wang & Min Y. Kim & Chibo Hong & Jennifer A. Doudna & Susan M. Chang & Joanna J. Phillips & David A. Solomon & Joseph F. Costello, 2022. "Conserved features of TERT promoter duplications reveal an activation mechanism that mimics hotspot mutations in cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Diletta Fontana & Ilaria Crespiatico & Valentina Crippa & Federica Malighetti & Matteo Villa & Fabrizio Angaroni & Luca De Sano & Andrea Aroldi & Marco Antoniotti & Giulio Caravagna & Rocco Piazza & A, 2023. "Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Leland S. Hu & Fulvio D’Angelo & Taylor M. Weiskittel & Francesca P. Caruso & Shannon P. Fortin Ensign & Mylan R. Blomquist & Matthew J. Flick & Lujia Wang & Christopher P. Sereduk & Kevin Meng-Lin & , 2023. "Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Pauline Latzer & Henning Zelba & Florian Battke & Annekathrin Reinhardt & Borong Shao & Oliver Bartsch & Armin Rabsteyn & Johannes Harter & Martin Schulze & Thomas Okech & Alexander Golf & Christina K, 2024. "A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    6. Mykhaylo Slobodyanyuk & Alexander T. Bahcheli & Zoe P. Klein & Masroor Bayati & Lisa J. Strug & Jüri Reimand, 2024. "Directional integration and pathway enrichment analysis for multi-omics data," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Osama Al-Dalahmah & Michael G. Argenziano & Adithya Kannan & Aayushi Mahajan & Julia Furnari & Fahad Paryani & Deborah Boyett & Akshay Save & Nelson Humala & Fatima Khan & Juncheng Li & Hong Lu & Yu S, 2023. "Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Ming Tang & Hussein A. Abbas & Marcelo V. Negrao & Maheshwari Ramineni & Xin Hu & Shawna Marie Hubert & Junya Fujimoto & Alexandre Reuben & Susan Varghese & Jianhua Zhang & Jun Li & Chi-Wan Chow & Xiz, 2021. "The histologic phenotype of lung cancers is associated with transcriptomic features rather than genomic characteristics," Nature Communications, Nature, vol. 12(1), pages 1-11, December.

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