10 times more accurate
A Cambridge University study has demonstrated a diagnostic test that can detect cancer at an early stage. To do this, the researchers performed personalized genetic testing of patients' tumors to find blood samples for hundreds of different genetic mutations in circulating tumor DNA, which is released by cancer cells into the bloodstream. Using a number of new methods of analyzing the data obtained to remove "background noise" and improve accuracy, the group has achieved a level of sensitivity that in some cases is able to detect one mutant molecule among a million DNA fragments. This test is about ten times more sensitive than existing methods.
Currently, personalized tests that can determine whether cancer is present or detect it at an early stage are being prepared for clinical trials. It may take several years before it is put into practice, but it is already known that the sensitivity of such tests is not maximum. A new test of the Cambridge group with increased sensitivity may replenish the arsenal of doctors in the near future.
Detection of circulating tumor DNA in blood samples (liquid biopsy) allows doctors to obtain more information about the properties of a patient's tumor without the need for invasive surgery. The technique is important for monitoring patients, especially after treatment, as an indicator of the effectiveness of therapy or the risk of relapses.
Currently, the sensitivity of early cancer diagnosis methods depends on the number of mutant DNA fragments, either relative to the background DNA, or in absolute measurement. When the level of circulating tumor DNA is too low, the test can give a negative result, even if cancer cells remain in the patient's body, which can lead to a relapse.
A single tumor contains several different mutations that led to the formation of cancer. Although some of them are widely known in certain types of cancer, for example, the epidermal growth factor receptor (EGFR) in lung cancer, the general set of mutations for a tumor varies from person to person. By analyzing the genetic structure of a human tumor and individually targeting a number of mutations, a liquid biopsy for cancer monitoring can become much more sensitive.
Until recently, personalized liquid biopsies detected from 10-20 to 100 mutations in the blood. In one sample, they can detect circulating tumor DNA if its level is not less than one per 30 thousand DNA fragments.
The new technique detects hundreds, and sometimes thousands, of mutations in each blood sample, usually detecting one mutant molecule per 100 thousand, and under optimal conditions, sensitivity can reach a level measured in single parts per million.
Researchers compare a traditional liquid biopsy to finding a needle in a haystack. In their new approach using personalized genetic profiles to search for multiple, not just one mutation, they increase the number of "needles" that can be found, increasing the likelihood of success.
The authors also claim that the "haystack" itself can be reduced: the methods developed for this study require less blood. If the technology is improved, diagnostic tests will be created, for which literally one drop of blood is enough. Patients will be able to perform the injection independently at home, and then send the material to the laboratory for analysis. This will reduce the number of clinic visits and allow you to monitor the patient more often.
The researchers studied samples from 105 people with cancer and tested the method on small groups of patients with five different types of cancer, both with early and late stages of the disease.
The test showed confident results and was able to detect circulating tumor DNA in patients with advanced breast cancer and melanoma, as well as with glioblastoma, which is known to be difficult to diagnose by blood. The new test was also able to detect tumor DNA in patients with early-stage lung and breast cancer, as well as with early-stage operated melanoma, when the level of tumor DNA in the blood is much lower and difficult to determine.
The researchers plan to use their method to measure the levels of circulating tumor DNA in individuals at high risk of developing cancer in order to maximize the accuracy of tests for early detection of cancer.
The article by J.C.M.Wan et al. ctDNA monitoring using patient-specific sequencing and integration of variant reads is published in the journal Science Translational Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Cambridge: Blood test to monitor cancer up to ten times more sensitive than current methods.