4 days Ago
Mayo Clinic researchers have developed an innovative testing strategy for mesothelioma that could potentially increase the detection rate of cancer DNA in the blood. This approach focuses on shuffled or swapped sections of DNA in mesothelioma cancer cells, called chromosomal rearrangements. By detecting these complex DNA patterns, rather than just single-point mutations, the method could lead to earlier diagnoses and new avenues for targeted therapies.
"We're pushing the frontiers of what's possible in blood-based monitoring," says Aaron Mansfield, M.D., a medical oncologist and lead author of the study at the Center for Individualized Medicine and the Mayo Clinic Comprehensive Cancer Center.
"Improving detection rates could offer insights into monitoring patients' responses to therapy and detecting recurrence after surgery." Mesothelioma is a rare cancer that develops in the thin membranes that line the chest and abdomen, most commonly caused by inhaling asbestos fibers . These fibers are often found in insulation, vinyl tiles, roofing materials and paint.
Despite decades of regulations to limit asbestos exposure, approximately 3,000 people in the U.S. are diagnosed with mesothelioma each year, according to the American Cancer Society.
Mesothelioma typically exhibits a low number of single-point genetic mutations , making it difficult to detect with traditional blood tests. However, the presence of chromosomal rearrangements —like shuffling words in a sentence—provides a new diagnostic target. This differs from many other cancers that often rely on detecting single-point mutations—tiny changes in the DNA sequence, similar to altering a single letter in a word.
In the proof-of-concept study , published in the Journal of Thoracic Oncology Clinical and Research Reports , Dr. Mansfield and his team used whole genome sequencing to locate key chromosomal changes in the DNA of cancer cells. Next, they created tiny pieces of DNA, called primers, that they designed in the lab to precisely match and attach to these chromosomal changes.
They then searched for these changes in blood. This combination of cutting-edge tools allowed the researchers to create personalized tests that detect and track cancer DNA in each patient's blood. The findings build on the team's previous mesothelioma research, including a study that identified a genomic signature to predict which patients with mesothelioma could benefit from immunotherapy.
Additionally, Dr. Mansfield's previous research shows how chromosomal rearrangements have neoantigenic potential, meaning they can help the body make an immune response against cancer cells. The team plans to expand this study to include more patients and further refine the testing method.
More information: Kaushal Parikh et al, Individualized Cell-Free DNA Monitoring With Chromosomal Junctions for Mesothelioma, JTO Clinical and Research Reports (2024). DOI: 10.1016/j.
jtocrr.2024.100692.
