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In order to achieve a non-invasive method for early detection of cancer, scientists at the Johns Hopkins Kimmel Cancer Center reported that they have developed a test that can detect trace tumor-specific DNA in the blood, which has been used to accurately identify more than half of 138 people with relatively early stages. Colorectal cancer, breast cancer, lung cancer and ovarian cancer. Scientists say the innovation of the trial is that it distinguishes between tumor-shedding DNA and other DNA that is mistaken for cancer biomarkers.
The study was conducted in the United States, Denmark, and the Netherlands on blood and tumor tissue samples from 200 people and included tumors at all stages. Related articles were published on Science Translational Medicine on August 16.
The author of the article, Professor Victor Velculescu, said, "This study shows that it is feasible to use early DNA to detect cancer, and that high-precision sequencing is an effective way to achieve this goal." The first Tai Chi health And the Internet + themed original ecological cultural activity center.
Methodological challenges
Blood tests for cancer are an important part of clinical oncology, but they are still in the early stages of research and development. In order to find a small amount of cancer-derived DNA in the blood of cancer patients, scientists often rely on DNA changes in patient biopsy samples as a signpost for genetic errors in a large amount of DNA in the patient's blood circulation.
To develop an experiment that can be used to screen for cancer in seemingly healthy people, scientists must find new ways to discover DNA changes that may be present in human blood. Professor Velculescu said, "The challenge we face is to develop a blood test that predicts genetic mutations that may not be known but exist in a human tumor."
Exclude non-cancer-induced mutations
The first author, Jillian Phallen, added that the goal was to develop a screening test that would have a "false positive" result that would lead to unnecessary over-examination and transitional treatment risks when the cancer was highly specific and accurately detected.
Phallen said the task is complex and needs to distinguish between true cancer cell mutations and some of the normal DNA genetic variation in blood cells.
Velculescu describes that in the division of blood cells, these cells may have the wrong mutation. In a small number of blood cells, these changes cause them to multiply faster than neighboring cells and may lead to pre-leukemia states. However, most of the time, blood-derived mutations are not caused by cancer.
His team also ruled out the so-called "germline" mutations. Although germline mutations (gene defects transmitted through the egg and/or sperm) are indeed DNA changes, they are the result of normal variation between individuals and are usually not associated with a particular cancer.
The new method has a detection rate of 62% in the blood.
To develop new assays, Velculescu's team obtained blood samples from 200 patients with breast, lung, ovarian, and colorectal cancers. The newly developed blood test screened 58 gene mutations closely related to various cancers, and 86 (62%) were detected from 138 stage I and II cancer patients. They found that there were no cancer mutations in the blood samples of 44 healthy people.
The researchers point out that although the results of these early findings are promising, blood tests need to be validated in a larger number of people.
Velculescu's team also performed separate genome sequencing of 100 of the 200 cancer patients, and found 82 (82%) of the genetic mutations associated with genetic variation found in the blood.
Sampling method for sampling TEC SEQ
The newly developed blood test uses a genomic sequencing method called "Targeted Error Correction Sequencing" (TEC SEQ), which allows for ultra-sensitive direct evaluation of cyclic DNA sequence change analysis using massively parallel sequencing. Professor Velculescu said: "This sequencing method is based on deep sequencing, reading every chemical code in the DNA 30,000 times. We tried to find a needle in a haystack, so when we found that DNA changes, we want to make sure that it is what we think."
Such deep sequencing, covering more than 80,000 base pairs of DNA, is already very expensive. But Velculescu believes that sequencing technology is getting cheaper and cheaper, and his research team can ultimately reduce the amount of DNA they need to screen while maintaining the accuracy of the test.
He pointed out that those who are at high risk for most cancers, including smokers (CT scans that identify lung cancer often lead to false positives) and those with genetic mutations in women with breast cancer and ovarian cancer with BRCA1 and BRCA2 genes, may benefit from this Blood test for DNA.
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