Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes

Farshad Nassiri ^1,2, Ankur Chakravarthy ³, Shengrui Feng ^3,4

¹MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada.
²Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
³Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
⁴Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
⁵Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁶Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁷Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁸MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada. gelareh.zadeh@uhn.ca.
⁹Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. gelareh.zadeh@uhn.ca.
¹⁰Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. daniel.decarvalho@uhnresearch.ca.
¹¹Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. daniel.decarvalho@uhnresearch.ca.

⁰MacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario, Canada.

Nature Medicine +

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June 24, 2020

View abstract on PubMed

Summary

Diagnosing brain tumors noninvasively is now possible. DNA methylation analysis in plasma can detect and differentiate common intracranial tumors, avoiding risky surgery.

Area Of Science

Neuro-oncology
Molecular diagnostics
Genomics

Background

Definitive diagnosis of intracranial tumors currently requires invasive surgical biopsies.
Noninvasive diagnostic methods are sought to reduce surgical risks and improve patient outcomes.
Distinguishing between certain primary intracranial tumors can be challenging with conventional imaging techniques.

Purpose Of The Study

To evaluate the efficacy of plasma-derived DNA methylation profiling for the noninvasive detection and classification of primary intracranial tumors.
To determine if this method can accurately differentiate tumors with similar origins that are difficult to distinguish via standard imaging.

Main Methods

Analysis of cell-free DNA (cfDNA) methylation patterns in patient plasma samples.
Development and application of specific DNA methylation signatures for tumor detection.
Comparison of methylation profiles against established diagnostic criteria and imaging results.

Main Results

Plasma DNA methylation profiles demonstrated highly specific signatures for common primary intracranial tumors.
The method accurately discriminated between tumor types, including those with shared cell-of-origin lineages.
The diagnostic performance was robust even for tumors challenging to distinguish using standard-of-care imaging.

Conclusions

Noninvasive diagnosis of intracranial tumors is feasible using plasma DNA methylation analysis.
This approach offers a promising tool for accurate tumor detection and differentiation, potentially reducing the need for invasive procedures.
Methylation profiling represents a significant advancement in neuro-oncology diagnostics.