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Li-Fraumeni syndrome is an inherited condition associated with a very high risk of developing tumors affecting the breast, soft tissue, brain, and other organs.
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Blood Test to Detect Cancer Early in High-Risk Families

Liquid biopsies help extract and screen circulating tumor DNA for cancer-causing anomalies well in advance

The Hospital for Sick Children

The Hospital for Sick Children (SickKids), affiliated with the University of Toronto, is Canada's most research-intensive hospital and the largest centre dedicated to improving children's health in the country.

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Published:Oct 25, 2023
|2 min read
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Researchers from The Hospital for Sick Children (SickKids), the Ontario Institute for Cancer Research (OICR), and the University Health Network (UHN) have demonstrated that by analyzing patients’ blood samples, they are able to detect cancer earlier in individuals with Li-Fraumeni syndrome—an inherited condition with an almost 100 percent lifetime risk of developing cancer. The research, led by Trevor Pugh, PhD, FACMG, and Raymond Kim, MD, PhD, has been published recently in Cancer Discovery

What happens in Li-Fraumeni syndrome?

Li-Fraumeni syndrome is an inherited condition associated with a very high risk of developing cancer—often tumors affecting the breast, soft tissue, brain, and other organs. It is caused by changes in the TP53 gene, which encodes a protein that helps to prevent tumor formation and is commonly termed the “guardian of the genome.”

Cancerous cells and healthy cells release pieces of DNA into the blood, which is called circulating tumor DNA (ctDNA). By analyzing these DNA fragments, researchers are developing methods to detect whether a tumor has developed in the body. Testing blood samples for signs of cancer—often called liquid biopsies—is an attractive screening approach compared to imaging methods, which require specialized machines, and biopsies, which are more invasive.

The research team analyzed 170 blood samples from 82 individuals with Li-Fraumeni syndrome collected over several years, as well as 30 blood samples from individuals without Li-Fraumeni syndrome, providing a proof-of-principle framework that may support the detection of specific cancers earlier for individuals with Li-Fraumeni syndrome.

“We used a combination of genomic, fragmentomic, and epigenetic methods to analyze patients’ blood samples at a molecular level,” says Pugh, senior scientist at Princess Margaret Cancer Centre and director of the Ontario Institute for Cancer Research (OICR) Genomics Program, where blood samples were analyzed. “The key to these long, multi-year studies is keeping up the momentum and building infrastructure to enable comparisons of multiple types of data over time. Here, we were able to detect multiple different types of DNA changes in blood that were a telltale sign that cancer was developing somewhere in the body months before cancer would show up in imaging.”

Impact of early detection: A case study

For Luana Locke and her family, early detection is invaluable and has prolonged her life many times already. Locke was diagnosed with breast cancer at age 25 and later discovered that her mother, children, and many members of her extended family carried the same TP53 mutation.

Locke, who has since had sarcoma, lung cancer, thyroid cancer, and skin cancer, and her children have regular screenings, blood tests, MRIs of the entire body, and ultrasounds at Princess Margaret Cancer Centre and SickKids to detect cancers early. After years of these scans Locke’s daughter, Juliet, was diagnosed with leukemia at age 14, a condition they have since learned may have been detected months earlier with this new blood sample analysis. “Even though I have LFS, I never really felt cancer anxiety until after I was diagnosed,” says Juliet. “While my check-ups are reassuring, getting more precise diagnoses earlier is the next level of care.”

The team will conduct a clinical trial to further test this approach and screen patients in the hope of finding their cancer earlier. These patients will include those with different types of high-risk cancer predisposition syndromes, including Li-Fraumeni syndrome, Lynch Syndrome, and Hereditary Breast and Ovarian Cancer—all of which are under a nationwide research consortium that Pugh and Kim founded in 2017.

- This press release was originally published on The Hospital for Sick Children (SickKids) website