Detection of Brain Cancer Using Genome-wide Cell-free DNA Fragmentomes.

Journal: Cancer discovery
Published Date: Aug 4, 2025

Abstract

UNLABELLED: Diagnostic delays in patients with brain cancer are common and can impact patient outcome. Development of a blood-based assay for detection of brain cancers could accelerate brain cancer diagnosis. In this study, we analyzed genome-wide cell-free (cfDNA) fragmentomes, including fragmentation profiles and repeat landscapes, from the plasma of individuals with (n = 148) or without (n = 357) brain cancer. Machine learning analyses of cfDNA fragmentome features detected brain cancer across all-grade gliomas (AUC = 0.90; 95% confidence interval, 0.87-0.93), and these results were validated in an independent prospectively collected cohort. cfDNA fragmentome changes in patients with gliomas represented a combination of fragmentation profiles from glioma cells and altered white blood cell populations in the circulation. These analyses reveal the properties of cfDNA in patients with brain cancer and open new avenues for noninvasive detection of these individuals.

Authors

  • Dimitrios Mathios
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Noushin Niknafs
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
  • Akshaya V Annapragada
    Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
  • Ernest J Bobeff
    Department of Neurosurgery and Neurooncology, Medical University of Lodz, Barlicki University Hospital, Lodz, Poland.
  • Elaine J Chiao
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Kavya Boyapati
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Keerti Boyapati
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Sarah Short
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Adrianna L Bartolomucci
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Stephen Cristiano
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Shashikant Koul
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Nicholas A Vulpescu
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Leonardo Ferreira
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Jamie E Medina
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Daniel C Bruhm
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Vilmos Adleff
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Małgorzata Podstawka
    Department of Neurosurgery and Neurooncology, Medical University of Lodz, Barlicki University Hospital, Lodz, Poland.
  • Patrycja Stanisławska
    Department of Neurosurgery and Neurooncology, Medical University of Lodz, Barlicki University Hospital, Lodz, Poland.
  • Chul-Kee Park
    Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Judy Huang
    Department of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
  • Gary L Gallia
    Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Henry Brem
    Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Debraj Mukherjee
    Department of Neurosurgery, Johns Hopkins University School of Medicine, 1800 Orleans Street, Baltimore, 21287, MD, USA.
  • Justin M Caplan
    Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Jon Weingart
  • Christopher M Jackson
    Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Michael Lim
    Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD.
  • Jillian Phallen
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Robert B Scharpf
    Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Victor E Velculescu
    The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. velculescu@jhmi.edu angiuoli@personalgenome.com.

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