Searching the Blood for Cancer

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Ground-breaking findings set the stage for blood tests to diagnose brain and kidney cancers.
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Instead of using a traditional biopsy, which requires an invasive procedure to collect a tissue sample, liquid biopsy uses a blood sample to diagnose disease. The lead author of the study, Dr. De Carvalho, is pictured on the right.

Can you diagnose cancer with a blood test? The answer is now yes for brain and kidney tumours, according to new research from UHN and Harvard Medical School.

Published in the latest issue of Nature Medicine, the tests were developed based on findings by Dr. Daniel De Carvalho, a Senior Scientist and Canada Research Chair at Princess Margaret Cancer Centre.

His research group studies a genetic change known as DNA methylation—a process through which the cell attaches a chemical group known as methyl to DNA. This process can change cell behaviour by affecting which genes get turned on or off. In cancer cells, DNA methylation patterns are disrupted and lead to unregulated cancer growth.

“We took advantage of the fact that there are hundreds of thousands of DNA fragments from cancer cells circulating in the blood,” says Dr. De Carvalho. “Using this knowledge, we developed advanced approaches to profile or ‘read’ DNA methylation in this circulating DNA and combined them with machine learning analysis.” The result: a highly sensitive test that can classify multiple solid tumours, including brain and kidney cancers.

The approach was applied to brain cancer, through a collaboration with Dr. Gelareh Zadeh, Senior Scientist at the Princess Margaret Cancer Centre and Medical Director of the Krembil Brain Institute.

The team analyzed blood samples paired with brain cancer tumour samples. Machine learning was used to analyze DNA methylation in the blood samples and to classify the brain tumour type.

"Because this test is so sensitive in picking up even small amounts of highly specific tumour-derived signals in the blood, we now have a new, non-invasive way of detecting and discriminating between common brain tumours—something which was long thought impossible,” says Dr. Zadeh.

To apply the approach to detect kidney cancer, Dr. De Carvalho worked with Drs. Toni Choueiri and Matthew Freedman at the Dana-Farber Cancer Institute in Boston.

The team reported accurate classification of all the various stages of kidney cancer using blood plasma and demonstrated that the method could also be applied to urine samples to identify individuals with renal cell carcinoma—the most common type of kidney cancer in adults.

"DNA methylation is a type of epigenetic change that, unlike mutations or other genetic changes, does not alter the sequence of the DNA. Our findings reveal that these epigenetic changes represent a powerful tool in the fight against cancer—one that could be combined with traditional genetic testing to develop more accurate and more sensitive cancer tests,” says Dr. De Carvalho.

These findings lay the groundwork for the development of blood tests, which are less invasive than traditional biopsies, to detect and diagnose kidney and brain cancers. Future work will validate these findings clinically and explore the application of this strategy to other solid tumours.

Nassiri F, Chakravarthy A, Feng S, et al. Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes. Nat Med. 2020 Jun 22. doi:10.1038/s41591-020-0932-2. This work was supported by the Canadian Institutes of Health Research, the Brain Tumour Charity (UK), the Princess Margaret Cancer Foundation, the Natural Sciences and Engineering Research Council of Canada and the Province of Ontario. D De Carvalho holds a Tier 2 Canada Research Chair in Neoplasms.

Nuzzo PV, Berchuck JE, Korthauer K, et al. Detection of renal cell carcinoma using plasma and urine cell-free DNA. Nat Med. 2020 Jun 22. doi:10.1038/s41591-020-0933-1. This work was supported by Rebecca and Nathan Milikowsky, Dana-Farber Cancer Institute, H.L. Snyder Medical Foundation, BC Children’s Hospital Research Institute, BC Provincial Health Services Authority, Children’s & Women’s Health Centre of British Columbia, BC Children’s Hospital Foundation and the Canadian Institutes of Health Research.

Dr. Gelareh Zadeh, Senior Scientist at the Princess Margaret Cancer Centre.