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Precision diagnosis and prognosis of primary and metastatic brain tumours using DNA methylation profiling in liquid biopsy

Principal Investigator:
  • Gelareh Zadeh, University Health Network, Princess Margaret, University of Toronto
Team Members:
  • Kenneth Aldape, Princess Margaret Centre - UHN
  • Daniel De Carvalho, Princess Margaret center - UHN
  • Canadian Cancer Society
  • Canadian Institutes of Health Research

Project Overview

Need for project: More sensitive molecular tools are needed in the field of neuro-oncology to enable early detection, more accurate diagnosis, and prediction of outcome for brain tumors. We have early experience in establishing that DNA methylome signatures in liquid biopsy can be used as a highly sensitive approach for the diagnosis and prognosis of brain tumors. We believe it is now a top priority to build on these results to extend to all common brain tumor types – gliomas and brain metastases.

Goal of project: Our goal is to develop a DNA-methylation based nomogram using the primary cancer methylation signature to be able to predict the likelihood of brain metastasis in patients with breast, lung, or melanoma tumors. As a second goal, we will focus refining our cfDNA methylome analysis to develop a tool that enables prediction of glioma progression to higher gradem as well as early detection of tumor recurrence after therapy.

Project description: We will obtain the methylation signature of the three most common cancer types that metastasize to the brain, breast, lung, and melanoma and use the methylome to develop a nomogram that can predict metastasis to the brain. We will collect serial plasma samples from glioma patients over 1-5 years to analyze the serial time points the content and methylation signature of cell-free DNA that would predict the likelihood of glioma progression to a higher grade and recurrence.

Future impact: The results of this project will enable non-invasive prediction of brain metastases as well as early detection of tumor recurrence or response to therapy in gliomas.