Announced on Dec 14, 2018
Cancer scientists led by Dr. Daniel De Carvalho at the Princess Margaret Cancer Centre have developed a blood test that can detect and classify cancer at its earliest stages.
The findings, published in Nature, describe a potential way to detect cancer earlier when it is more easily treated and long before symptoms appear.
Cancer cells develop a number of changes in their DNA that allow them to grow unimpeded. These changes accumulate over time and become easier to detect as the cancer progresses. The researchers took advantage of a particular type of change to the DNA known as an epigenetic change. These changes, rather than changing the code, chemically modify letters of the code.
"A major problem in cancer is how to detect it early. Finding that one-in-a-billion cancer-specific mutation in the blood, especially at earlier stages, where only a few genetic errors are present, is difficult,” says Dr. De Carvalho. “Epigenetic changes, which do not alter the underlying DNA sequence, are not similarly constrained and could provide an alternative method of detecting cancer.”
His team recently profiled thousands of these epigenetic modifications in lung, pancreatic, colorectal, breast, bladder and kidney cancers as well as health control and leukemia patients. They then used the data to predict the presence of cancer DNA in the blood.
The scientists discovered that epigenetic modifications in blood DNA could be used to accurately detect and classify tumours. They have since expanded this research and successfully matched more than 700 tumour and blood samples in a wide variety of cancer types.
Beyond the lab, next steps include analysing data from large research studies already under way in several countries, where blood samples were collected months to years before cancer diagnosis. These studies will help to determine whether the test can be used clinically to screen for cancer.
The work was supported by University of Toronto's McLaughlin Centre, Canadian Institutes of Health Research, Canadian Cancer Society, Ontario Institute for Cancer Research through the Province of Ontario, and The Princess Margaret Cancer Foundation. Dr. De Carvalho holds a Tier 2 Canada Research Chair (CRC) in Cancer Epigenetics and Epigenetic Therapy and Dr. Pugh holds a Tier 2 CRC in Translational Genomics.
Shen SY, Singhania R, Fehringer G, Chakravarthy A, Roehrl MHA, Chadwick D, Zuzarte PC, Borgida A, Wang TT, Li T, Kis O, Zhao Z, Spreafico A, Medina TDS, Wang Y, Roulois D, Ettayebi I, Chen Z, Chow S, Murphy T, Arruda A, O'Kane GM, Liu J, Mansour M, McPherson JD, O'Brien C, Leighl N, Bedard PL, Fleshner N, Liu G, Minden MD, Gallinger S, Goldenberg A, Pugh TJ, Hoffman MM, Bratman SV, Hung RJ, De Carvalho DD. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature. 2018 Nov;563(7732):579-583. doi: 10.1038/s41586-018-0703-0.